Integrated robotic sample transfer device

ABSTRACT

Embodiments include integrated robotic sample transfer devices and components thereof which are used for reliably and accurately transferring small samples of material from one registered position to another registered position. Such transfers of material may be carried out by a single pin tool or an array of pin tools of a pin tool head assembly of robotic sample transfer devices. Some embodiments also include automated cleaning of the pin tools used to transfer the sample material. Some embodiments are fully integrated units having internal fluid supply and waste tanks, vacuum source, fluid pumps, controllers and user interface devices.

RELATED APPLICATIONS

This application claims priority under 35 U.S.C. section 119(e) fromU.S. provisional application Ser. No. 60/972,879 filed Sep. 17, 2007, byR. Silbert et al. titled “Integrated Robotic Sample Transfer Device”which is incorporated by reference herein in its entirety.

FIELD OF THE INVENTION

Embodiments of the present invention generally relate to robotic sampletransfer devices and methods which may be used for reliably andconsistently transferring large numbers of small samples of materialfrom one registered position to another registered position. Suchtransfers of material may be carried out by a single pin tool or anarray of regularly spaced pin tools on a pin tool head assembly. Someembodiments include automated cleaning of the pin tools used to transferthe sample material between sample transfer steps.

BACKGROUND

In recent years, developments in the field of life sciences haveproceeded at a very rapid pace. Universities, hospitals and newly formedcompanies have made groundbreaking scientific discoveries and advancesthat promise to reshape the fields of medicine, agriculture, andenvironmental science. However, the success of these efforts depends, inpart, on the development of sophisticated laboratory tools that willautomate and expedite the testing and analysis of biological samples.Only upon the development of such tools can the benefits of these recentscientific discoveries be fully achieved.

At the forefront of these efforts to develop better analytical tools isan effort to expedite the analysis of complex biochemical structures.This is particularly true for human genomic DNA, which is comprised ofat least about one hundred thousand genes located on twenty fourchromosomes. Each gene codes for a specific protein, which fulfills aspecific biochemical function within a living cell. Changes in a DNAsequence are known as mutations and can result in proteins with alteredor in some cases even lost biochemical activities; this in turn cancause a genetic disease. More than 3,000 genetic diseases are currentlyknown. In addition, growing evidence indicates that certain DNAsequences may predispose an individual to any of a number of geneticdiseases, such as diabetes, arteriosclerosis, obesity, certainautoimmune diseases and cancer. Accordingly, the analysis of DNA is adifficult but worthy pursuit that promises to yield informationfundamental to the treatment of many debilitating and life threateningdiseases.

Analysis of DNA is made particularly cumbersome due to size and the factthat genomic DNA includes both coding and non-coding sequences (e.g.,exons and introns). As such, traditional techniques for analyzingchemical structures, such as the manual pipeting of source material tocreate samples for analysis, are of little value. To address the scaleof the necessary analysis, scientists have developed parallel processingprotocols for DNA diagnostics.

Robotic pin tool devices used for the accurate and efficient transfer ofmaterials from sample wells to sample test sites have been used for theprocessing of materials for a great variety of applications. Suchdevices are frequently used for the processing of fluid DNA samples formass spectrometry, including MALDI mass spectrometry, genotyping,quantitative gene expression including PCR methods, methylation analysisand SNP discovery. For such processes, a small amount of fluid is takenup by a pin tool from a pre-determined well of a microtiter plate andmapped and deposited to a pre-determined location on another surface,such as a mass spectrometry chip. The control software for the roboticsof the robotic pin tool generally will track the transfer of samplesfrom each well of the microtiter plate to the corresponding location onthe chip such that a comprehensive mapping of samples is maintained.Once a set of samples have been transferred, the pins may undergo awashing process and may then be used to transfer another set of samples.Such tools and processes greatly enhance the efficiency and reliabilityof sample handling and processing where a large number of small volumesamples need to be processed.

Current devices that perform these procedures are useful, but aregenerally large, heavy and expensive machines that require the use oflarge external fluid storage tanks, external computing devices,including desktop units with corresponding keyboard and monitor devices,external plumbing to facility utilities and the like. As a result, astandard pin tool sample transfer machine may take up a large amount ofspace within a laboratory in which it is being used. In addition,standard pin tool sample transfer devices may be inconvenient to operateand maintain. What has been needed is a robotic sample transfer machinethat is small in size and weight relative to existing machines and lessexpensive than the currently available sample transfer devices. What hasalso been needed is a robotic sample transfer device that is userfriendly, easy and reliable to operate and economical to maintain.

SUMMARY

Some embodiments of robotic sample transfer devices include asubstantially horizontal work surface and a three axis roboticpositioning assembly. The three axis robotic positioning assembly has afixed mount portion secured in fixed relation with the work surface, atranslatable carrier configured to be translatable in three differentaxes with respect to the fixed mount portion and working surface. Thethree axis robotic positioning assembly has a stepper motor andcorresponding linear encoder assembly for at least one axis. Acontroller is in communication with the stepper motor of each of thethree axes and linear encoder of the three axis robotic positioningassembly.

Some embodiments of a robotic sample transfer device include a housing,a substantially horizontal work surface disposed within the housing anda three axis robotic positioning assembly disposed within the housinghaving a fixed mount portion secured in fixed relation with the worksurface and a translatable carrier member translatable in threedifferent axes with respect to the fixed mount portion and work surface.The robotic sample transfer device also includes at least one pin toolcoupled to the translatable carrier having a shaft and a samplereservoir in a distal end of the shaft. A plurality of functionalelements may be disposed on the work surface having a nominal uppersurface at substantially the same z-axis height. The robotic sampletransfer assembly may also include a controller operatively coupled tothe three axis robotic positioning assembly.

For some embodiments, the functional elements disposed on the worksurface include a vacuum drying station, a fluid rinse station, aself-leveling ultrasonic cleaning well, a microtiter plate having anarray or regularly space sample supply wells and a chip having an arrayof regularly spaced sample deposition sites. For some embodiments, thecontroller of the robotic sample transfer device includes at least oneprocessor which is disposed within the housing at a level which is abovethe level of the work surface.

Some embodiments of an integrated robotic sample transfer device includea housing, a substantially horizontal work surface and a three axisrobotic positioning assembly disposed within the housing. The three axisrobotic positioning assembly may include a fixed mount portion, atranslatable carrier which is translatable in three different axes withrespect to the fixed mount portion, and a stepper motor for each axis.Some embodiments may include a linear encoder for at least one of theaxes. A pin tool head assembly may be secured to the translatablecarrier member and have an array of regularly spaced pin tools whichhave sample reservoirs disposed in the distal ends thereof and which areconfigured for axial displacement relative to a pin head body secured tothe translatable carrier of the three axis robotic positioning assembly.The substantially horizontal work surface is disposed within the housingand is secured in fixed relation to the fixed mount portion of the threeaxis positioning assembly. The work surface may have a plurality offunctional components disposed thereon which may include a fluid rinsestation, a vacuum drying station including a plurality of regularlyspaced vacuum drying ports corresponding to the regular spacing of thearray of pin tools, a self-filling ultrasonic cleaning well and amicrotiter plate mount block. The microtiter plate mount block isconfigured to releasably secure a pre-selected microtiter plate samplewell thereto. A chip mount block may also be disposed on the worksurface and have a nominal upper surface at substantially the same levelas at least one or more of the functional components. A controllerincluding a processor is disposed within the housing at a position whichis above the level of the work surface. A rinse fluid supply tank is influid communication with the fluid rinse station and disposed within thehousing. A waste water tank is in fluid communication with an overflowbasin of the fluid rinse station and disposed within the housing. Avacuum source is in fluid communication with the vacuum drying stationand an ultrasonic cleaning fluid supply reservoir is in fluidcommunication with the self-filling ultrasonic cleaning well.

Some embodiments of a method of registering a position of a pin toolhead assembly of a robotic sample transfer device relative to sampledeposition sites on a chip include providing a robotic sample transferdevice having a work surface with a plurality of functional elements, atleast two of which have a nominal upper surface at substantially thesame level. For some embodiments, a nominal upper surface of all thefunctional elements may be at the same z-axis level. For someembodiments, the functional elements that require a substantiallyprecise positional alignment of pin tools being used at the functionalelement may be at substantially the same z-axis level. The roboticsample transfer device may also have a three axis positioning systemwith a camera secured to a translatable carrier thereof and the pin toolhead assembly secured to a translatable carrier thereof. The nominalupper surfaces of functional components disposed on work surface areimaged by the camera and the image data of the nominal upper surfaces ofthe functional elements processed by an image processor to determine theapproximate position of the pin tool head assembly relative to thefunctional elements. The approximate position data is then used to movethe field of view of the camera to a first chip having an array ofregularly spaced sample deposition sites and an array of regularlyspaced fiducial marks disposed between the sample deposition sites. Thefiducial marks on the first chip are imaged by the camera and the imagedata of fiducial marks on the first chip processed by an imageprocessor. Feedback may then be obtained regarding a position of the pintool head assembly from one or more linear encoders of three axes of athree axis robotic positioning system. Linear encoder feedback may thenbe compared with image processing feedback and look up table data todetermine the precise position of the pin tools of the pin tool headassembly with respect to the sample deposition sites on the first chip.For some embodiments, the process may be repeated for two or more chipsto determine the position of the pin tools of the pin tool head assemblywith respect to sample deposition sites of the two or more chips.

Some embodiments of a method of dispensing calibration material onto achip include providing a chip having a first array of regularly spacedsample deposition sites disposed on a substantially flat working surfacethereof and at least one sample deposition site for receivingcalibration material which is also disposed on the flat working surfaceof the chip and which is off pitch with respect to the regular spacingof the array of regularly spaced sample deposition sites of the chip. Arobotic sample transfer device is provided which has a pin tool headassembly with an array of regularly spaced pin tools having distal endswhich are substantially coplanar with each other in a relaxed state. Theregular spacing of the pin tools corresponds to the regular spacing ofthe first array of sample deposition sites or an integer multiplethereof and is configured to align with the array of regularly spacedsample deposition sites of the chip or a subset thereof. Samplereservoirs of the pin tools of the array of regularly spaced pin toolsof the robotic sample transfer device are loaded with calibrationmaterial. Calibration material is dispensed from the pin tools of therobotic sample transfer device to the at least one sample depositionsite for receiving calibration material such that the pin tools whichare not aligned with sample deposition sites for receiving calibrationmaterial are off pitch with respect to the first array of regularlyspaced sample deposition sites of the chip and do not contact any of theregularly spaced sample deposition sites of the first array. For someembodiments, the chip may include a second array of regularly spacedsample deposition sites for receiving calibration material sample whichare off pitch with respect to the first array of regularly spaced sampledeposition sites. For such embodiments, calibration material from samplereservoirs of the pin tools of the robotic sample transfer device may bedispensed to the second array of sample deposition sites for receivingcalibration material such that the pin tools which are not aligned withsample deposition sites for receiving calibration material of the secondarray are off pitch with respect to the first array of regularly spacedsample deposition sites of the chip and do not contact any of theregularly spaced sample deposition sites of the first array.

Some embodiments of a pin tool displacement block for selectivelydisplacing at least one pin tool of a pin tool head assembly of arobotic sample transfer device include a block body portion having a topsurface and a bottom surface which is substantially parallel to the topsurface and a plurality of parallel slots formed into the block bodyportion. The pin tool displacement block also includes one or morerelieved portions in the slots corresponding to the location of pinsthat are to remain in use when the pin tool displacement block isengaged with the pin tools of the pin tool head. For some embodiments,the parallel slots formed into the body portion have a width to allowpassage and movement of a pin tool shafts but not a collar membersecured to the pin tool shaft so as to displace the pin in a retractedposition. Relieved portions in the slots are configured to allow passageand movement of the collar members so as not to displace thecorresponding pin tools in a retracted position located in positionscorresponding to pin tools which are to remain usable after deploymentof the block in a pin tool head assembly. Some embodiments of the pintool displacement block have a reversible configuration wherein when theblock is oriented in a first direction a first set of pins or pin isactive and oriented a second way a second set of pins or pin is activewhich is different from the first set.

Some embodiments of a method for selectively displacing at least one pintool of a pin tool head assembly of a robotic sample transfer device,include providing a pin tool displacement block with a block bodyportion having a top surface and a bottom surface which is substantiallyparallel to the top surface, a plurality of parallel slots formed intothe block body portion and one or more relieved portions in the slotscorresponding to the location of pins that are to remain in use when thepin tool displacement block is engaged with the pin tools of the pintool head. An array of pin tools of a pin tool head assembly aredisplaced by depressing the pin tools against a flat surface. The pintool displacement block is deployed into the pin tool head assembly suchthat the parallel slots of the pin tool displacement block slide overrows of the array of pin tools of the pin tool head assembly and the pintools are allowed to return to a relaxed state by retracting the pintool head assembly from the flat surface.

Some embodiments of a method of dispensing calibration material onto achip may include providing a chip having an array of regularly spacedsample deposition sites disposed on a substantially flat working surfacethereof. The chip may also haveat least one sample deposition site forreceiving calibration material which is also disposed on the flatworking surface of the chip. A robotic sample transfer device may beprovided having a pin tool head assembly with an array of regularlyspaced pin tools having distal ends which are substantially coplanar ina relaxed state and which have a regular spacing which is the same asthe regular spacing of the first array of sample deposition sites or aninteger multiple thereof. The pin tools of the pin tool head assemblymay be configured to align with the array of regularly spaced sampledeposition sites of the chip or a subset thereof. At least one of thepin tools of the pin tool head assembly may be axially displaced with apin tool displacement block and a sample reservoir of at least oneun-displaced pin tool of the robotic sample transfer device loaded withcalibration material. Calibration material may be dispensed from the atleast one un-displaced pin tool of the robotic sample transfer device tothe at least one sample deposition site for receiving calibrationmaterial such that the pin tools which are displaced by the pin tooldisplacement block do not contact the chip.

These features of embodiments will become more apparent from thefollowing detailed description when taken in conjunction with theaccompanying exemplary drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of an embodiment of a robotic sampletransfer device.

FIG. 2 is a rear elevation view with a rear panel of the housing notshown.

FIG. 3 is a front elevation view of the robotic sample transfer deviceof FIG. 1 with the processing chamber cover and tank chamber front covernot shown.

FIG. 4 is a perspective view of a three axis positioning system and worksurface of the robotic sample transfer device of FIG. 1.

FIG. 5 is a perspective view of an x-axis translation assembly of thethree axis positioning system.

FIG. 6 is a perspective view of the y-axis carrier and z-axis carrier ofthe three axis positioning system.

FIG. 6A is an enlarged view in partial section of a bottom plate, pintool shaft, helical spring clip and washer of a pin tool head assemblyembodiment.

FIG. 6B is a top view in partial section of a shaft of a pin tool insliding engagement with a cover plate.

FIG. 7 is a perspective view of a work surface and functional componentsof the robotic sample transfer device of FIG. 1.

FIG. 7A is an elevation view in partial section of an embodiment of awash fluid reservoir.

FIG. 7B is a transverse cross section of the wash fluid reservoir ofFIG. 7A taken along lines 7B-7B in FIG. 7A.

FIG. 7C is a perspective view of an embodiment of a calibration materialsupply vessel.

FIG. 7D is a perspective view of an embodiment of a calibration materialsupply vessel.

FIG. 8 is a top view of a work surface and functional components of therobotic sample transfer device of FIG. 1.

FIG. 9 is an exploded view of the work surface and functional componentsof the robotic sample transfer device of FIG. 1.

FIG. 10 is an elevation view of the work surface and functionalcomponents of the robotic sample transfer device of FIG. 1.

FIG. 11 is an enlarged perspective view of a ultrasound energy generatorof the ultrasonic cleaning well disposed on the work surface.

FIG. 11A is a top view of an embodiment of a chip having an array ofsample deposition sites disposed thereon.

FIG. 11B is a bottom view of the chip of FIG. 11A.

FIG. 12 is an elevation view of a pump housing with a rear cover of thehousing not shown for clarity of illustration.

FIG. 13 is a perspective view of a waste fluid tank.

FIG. 14 is a perspective view of a fluid supply tank.

FIG. 15 is a perspective view of a pin tool displacement block forselectively displacing a pin tool of a pin tool head assembly.

FIG. 15A is a sectional view of the block of FIG. 15 taken along lines15A-15A.

FIG. 16 is a top view of the pin tool displacement block of FIG. 15.

FIG. 17 is an elevation view of a pin tool head assembly embodimentincluding two spring loaded pin tools.

FIG. 17A is a front view of the pin tool head assembly of FIG. 17.

FIG. 18 is an elevation view of the pin tool head assembly of FIG. 17with the pin tools displaced in a proximal direction.

FIG. 19 is an elevation view of the pin tool head assembly with the pintool displacement block engaged.

FIGS. 20A-20D illustrate an embodiment of a pin tool displacement block,single pin configuration.

FIGS. 21A-21D illustrate an embodiment of a pin tool displacement block,six pin configuration.

FIG. 22 is a perspective view from a first side of a reversible pin tooldisplacement block embodiment.

FIG. 23 is an elevation view of the reversible pin tool displacementblock of FIG. 22.

FIG. 24 is a view from a second side of the reversible pin tooldisplacement block of FIG. 22.

FIG. 25 is an enlarged perspective view of a portion of a sample chipshowing sample deposition sites and sample reservoirs of a pin tool headassembly disposed over calibration sites.

FIGS. 26-34 show screen image representations of a graphic userinterface embodiment for communicating instructions and information to acontroller of a robotic sample transfer device.

FIGS. 35A-35D illustrate an embodiment of a pin tool displacement block,single pin configuration.

FIGS. 36A-36D illustrate an embodiment of a pin tool displacement block,six pin configuration.

FIGS. 37A-37C illustrate an embodiment of a pin protection block toolassembly.

FIG. 38A is a top view of an outer collar for use with a plungermechanism embodiment.

FIG. 38B is a cross section view of an outer collar for use with aplunger mechanism embodiment.

FIG. 39A is a front view of a plunger handle for use with a plungermechanism embodiment.

FIG. 39B is a cross section view of a plunger handle for use with aplunger mechanism embodiment.

FIGS. 40A-40C illustrate an embodiment of a dry station plate assembly,single in configuration.

FIGS. 41A-41C illustrate an embodiment of a dry station plate assembly,six pin configuration.

FIG. 42 illustrates the functional coupling of components which enableselective displacement of pin tools in the pin tool head.

DETAILED DESCRIPTION

As discussed above, currently available robotic sample transfer devicesare generally large, heavy and expensive machines that require the useof large external fluid storage tanks, external computing devices,including desktop units with corresponding keyboard and monitor devices,external plumbing to facility utilities and the like. As a result, astandard pin tool sample transfer machine may take up a large amount ofspace within a laboratory in which it is being used. In addition,standard pin tool sample transfer devices may be inconvenient andexpensive to operate and maintain.

As such, a robotic sample transfer device that is relatively small insize and weight may be particularly useful. In addition, a roboticsample transfer device that is user friendly, easy and reliable tooperate and can be simply maintained may also be particularly useful.Embodiments of robotic sample transfer devices described herein may bedirected to integrated configurations that have a relatively smallfootprint with internal storage tanks, internal controllers andprocessors, internal plumbing all disposed within a housing thatencloses a processing chamber. Such embodiments take up less laboratoryspace and are easy to use and maintain.

A graphic user interface may be disposed on an outer surface of thehousing of some embodiments which allows a user to easily program anduse the robotic sample transfer device while keeping the processingchamber closed. Embodiments of the graphic user interface may includetouch screen displays allowing intuitive user input without the need fora computer keyboard or mouse, although such alternative interface toolsmay be supported in some embodiments via USB ports or the like. Asubstantially horizontal work surface may include a plurality offunctional elements with two or more of the functional elements havingnominal upper surfaces at approximately the same level which allows animaging camera to easily image the functional elements of the worksurface as well as providing a work surface at a consistent level foreasy access and navigation. Such imaging of the functional elements maybe used or otherwise processed in some embodiments to quickly determinethe position of pin tools or pin tool head assemblies with respect tothe functional elements with a high degree of precision.

Some robotic sample transfer device embodiments may be used for theaccurate and efficient transfer of materials from one position toanother position may be useful for the processing of samples and thelike for a great variety of applications. Some embodiments may be usedfor the processing of fluid DNA samples for mass spectrometry, includingMALDI mass spectrometry, genotyping, quantitative gene expressionincluding PCR methods, methylation analysis and SNP discovery. Commonlyowned U.S. Pat. No. 6,730,517, filed Oct. 5, 2000 by Koster et al.,issued May 4, 2004, titled “Automated Process Line”, describes automatedmodular analytical systems and methods of analysis of samples and ishereby incorporated by reference herein in its entirety. Some or all ofthe robotic sample transfer device embodiments discussed herein may beconfigured to perform some or all of the analytical processes discussedin U.S. Pat. No. 6,730,517. Embodiments of the robotic sample transferdevice may be used to transfer samples that include liquids, solids,gels and the like, or any combination thereof.

Some robotic sample transfer device embodiments may include asubstantially horizontal work surface that has a plurality of functionalelements disposed on the work surface. The functional elements may beconfigured for the processing of small samples of material. A three axisrobotic positioning assembly may have a fixed mount portion which issecured in a fixed relation with the work surface to provide mobility oftools and other devices over and in contact with the work surface andfunctional elements thereof. The three axis robotic positioning assemblymay include one or more translatable carriers, at least one of which maybe configured to be translatable in three different axes with respect tothe fixed mount portion and working surface. For some embodiments, thethree different axes of the translatable carrier may be substantiallyorthogonal to each other. Certain tools or other devices may be securedto the translatable carrier in order to provide high precision mobilityof the tools and other devices with respect to the work surface andfunctional elements on the work surface. Some of the tools and devicesthat may be coupled to the translatable carrier include pin tools, pintool head assemblies, cameras, bar code readers and the like. For someembodiments, upper nominal surface or surfaces of the functionalelements may form the work surface.

While some translatable carrier embodiments may be movable and bepositioned in three axes, the three axis robotic positioning assemblymay include other translatable carrier embodiments, to which these sametools and devices may be coupled, that are moveable and may bepositioned in only one axis or two axes. The three axis roboticpositioning assembly may include a stepper motor for imparting motionand a corresponding linear encoder assembly for providing positionalfeedback or information for one or more of the three axes of the threeaxis robotic positioning assembly. As discussed above, one of the toolsthat may be moved in three axes above the work surface is a pin toolwhich may be coupled to the translatable carrier of the three axisrobotic positioning assembly. The pin tool may be coupled to thetranslatable carrier such that the pin tool is substantiallyperpendicular to the work surface. For embodiments that include a pintool head assembly, multiple pin tools of a pin tool head assembly whichis coupled to a translatable carrier may also be oriented substantiallyperpendicular to the work surface.

A controller may be used in communication, such as electrical or opticalcommunication, with the stepper motor and the linear encoder assembly ofone or more of the axes of the three axis robotic positioning assemblyin order to provide controllable movement to the one or more pin toolsor other devices coupled to the translatable carrier or carriers. Such acontroller may include one or more processors and data storage units incommunication with the processor or processors. Some controllerembodiments may also include one or more data input ports or terminalswhich allow a user to input data or other programming information inorder to have the controller carry out desired instructions orprocessing protocols. A graphic user interface on a housing of thedevice may be in communication with such a terminals or ports of thecontroller. Some embodiments of the robotic sample transfer device mayhave the controller and associated components and electronics of thecontroller disposed above the vertical level of the work surface toavoid damage to these components from spillage of liquids on or aroundthe work surface and associated functional components.

The controller may receive position data from the linear encoderassemblies as well as other sources and provide actuation signals andpower to the stepper motors of the three axes in order to producepredetermined motion and positioning of the translatable carrier andtools coupled thereto with respect to the work surface and functionalelements and with a high degree of precision. Position data generated byone of the linear encoder assemblies may include the position of atranslatable carrier relative to a corresponding rail member upon whichthe translatable carrier moves. For such embodiments, an optical linearencoder strip may be disposed on the rail member and be positioned to beread by a linear encoder reader disposed on the correspondingtranslatable carrier.

Sometimes a housing may be disposed about the work surface, three axisrobotic positioning assembly and controller as well as other componentsof robotic sample transfer device embodiments. Embodiments of thehousing may include a skin material disposed on a frame structure. Theskin material may be made of suitable polymers, composites, metals orthe like in order to provide an enclosed controlled processing chamberand to protect the components of the robotic sample transfer devicedisposed therein. As discussed above, a graphic user interface may bedisposed on or otherwise accessible from an exterior of the housing andbe operatively coupled to the controller for providing user input,instructions, data or the like to the controller.

Some embodiments of a robotic sample transfer device may include ahousing and a substantially horizontal work surface disposed within thehousing. A three axis robotic positioning assembly may also be disposedwithin the housing for such embodiments and have a fixed mount portionsecured in fixed relation with the work surface. The three axis roboticpositioning assembly may include one or more translatable carriermembers, including a translatable carrier member that is translatable inthree different axes with respect to the fixed mount portion and worksurface. At least one pin tool is coupled to the translatable carrier.The pin tool has a shaft and a sample reservoir in a distal end of theshaft. A variety of suitable reservoir embodiments may be used which maybe configured to draw and store small volume liquid samples, generallyin the nanoliter range of volume, into the reservoir by capillary actionor other suitable mechanisms.

A plurality of functional elements may be disposed on the work surfacewith each functional element having a nominal upper surface. For someembodiments, an upper nominal surface or surfaces of the functionalelements may form the work surface. For some embodiments, two or more ofthe nominal upper surfaces the functional elements may be disposed atsubstantially the same z-axis level or height. Such a configuration maybe useful in order to facilitate imaging of the functional elements andpositioning of the pin tool with respect to the nominal upper surface ofeach functional element. This may be particularly true in embodimentswherein an imaging camera is disposed on one or more of the translatablecarriers of the robotic positioning assembly and is used for imaging thefunctional elements disposed on the work surface.

For such embodiments, it may be useful to have the imaging cameradisposed on a translatable carrier embodiment that is translatable onlyin the X-Y plane, substantially parallel to the work surface. For such acamera with a fixed Z-axis position, the distance between the cameralens and the work surface or upper nominal surfaces of functionalelements disposed on the work surface may be substantially fixed. Thus,camera embodiments having a fixed focal length and narrow range of focusmay be positioned on the translatable carrier at the appropriate focaldistance from the work surface for consistent focused imaging of theupper nominal surfaces of the functional elements. In this way, theupper nominal surfaces of the functional elements disposed atsubstantially the same z-axis level will remain in focus and be clearlyimaged as the translatable carrier moves about over the work surface.The pin tool or other devices coupled to a translatable carrier whichmay be positioned in three axes may be moved independently of the camerain the Z-axis direction.

For some embodiments, the functional elements disposed on the worksurface may include a vacuum drying station, a fluid rinse station, aself-leveling gravity fed ultrasonic cleaning well, a microtiter platehaving an array or regularly space sample supply wells and a chip havingan array of regularly spaced sample deposition sites. A controller maybe operatively coupled to the three axis robotic positioning assembly aswell as any of the functional elements on the work surface or componentsthereof. Such a controller may include one or more processors and datastorage units in communication with the processor or processors whichare disposed within the housing at a level which is above the level ofthe work surface.

For some embodiments, the pin tool which is coupled to the translatablecarrier may be part of a pin tool head assembly having an array ofregularly spaced pin tools which is secured or otherwise coupled to thetranslatable carrier. For some embodiments, the vacuum drying stationmay include a plurality of regularly spaced vacuum drying portscorresponding to the spacing of the pin tools of the pin tool headassembly. For some embodiments, the fluid rinse station may includeindividual rinse tubes corresponding to each of the pin tools of thearray of regularly spaced pin tools of the pin tool head assembly.

For some embodiments, an ultrasonic cleaning fluid reservoir may bedisposed in fluid communication with the ultrasonic cleaning well. Theultrasonic cleaning fluid reservoir may have an enclosed and fluid tightinterior volume in fluid communication with a supply port configured tocouple in fluid communication to an inlet port of the ultrasoniccleaning well. For some embodiments of such a configuration, the supplyport of the ultrasonic cleaning fluid reservoir may be open to fluidflow when coupled into fluid communication with the inlet port of theultrasonic cleaning well and be substantially sealed when the removedfrom the inlet port of the ultrasonic cleaning well. Some particularembodiments may include a ball valve which is configured to seal thesupply port when the fluid reservoir is removed from the inlet port ofthe ultrasonic cleaning well.

Some embodiments of an integrated robotic sample transfer device mayinclude a housing and a three axis robotic positioning assembly disposedwithin the housing having a fixed mount portion and a translatablecarrier which is translatable in three axes with respect to the fixedmount portion and a substantially horizontal work surface. A steppermotor and corresponding linear encoder assembly may be included for oneor more of the axes of the three axis robotic positioning assembly. Eachstepper motor may be configured to provide motion in the direction ofeach respective axis and each linear encoder assembly may be used toprovide position data in the direction of each respective axis. A pintool head assembly may be secured to the translatable carrier memberwhich has an array of regularly spaced pin tools with sample reservoirsdisposed in the distal ends thereof. The pin tools may be configured foraxial displacement relative to a pin head body which is secured to thetranslatable carrier of the three axis robotic positioning assembly.Some embodiments of the robotic sample transfer device may also includea door on the housing which is configured to cover an opening to aprocessing chamber disposed within the housing.

The substantially horizontal work surface may be disposed within thehousing and secured in fixed relation to the fixed mount portion of thethree axis robotic positioning assembly. The work surface may have oneor more functional elements which may include a fluid rinse station, avacuum drying station including a plurality of regularly spaced vacuumdrying ports corresponding to the regular spacing of the array of pintools, a self-leveling ultrasonic cleaning well and a microtiter platemount block configured to releasably secure a sample well disposedthereon. For some embodiments, the upper nominal surfaces of two or moreof the functional elements may form the work surface. For some of theseembodiments, a nominal upper surface of the fluid rinse station, nominalupper surface of the vacuum drying station, nominal upper surface of theultrasonic cleaning well, nominal upper surface of a chip disposed inthe chip mount block and microtiter plate/sample well mounted in thesample well mount blocks are all disposed at substantially the samez-axis level. For some embodiments of the robotic sample transferdevice, the entire dry weight of the device is less than about 150pounds. For some embodiments, functional elements such as the ultrasoniccleaning well that do not require precise alignment in the x-y plane maybe disposed at a z-axis level that differs from the z-axis level of theremaining functional elements or subset of functional elements having anupper nominal surface disposed at substantially the same z-axis level.

A controller may be disposed within the housing. Such a controller mayinclude one or more processors and data storage units in addition to anassembly of other electronics and logic circuits in communication withthe processor or processors which may be disposed within the housing ata level which is above the level of the work surface. The controller,electronics associated with the controller as well as other componentsof the robotic sample transfer device may be powered by a universalpower supply in communication with the controller that produces aconstant or substantially constant output voltage with varied inputvoltages. Such a universal power supply may allow the robotic sampletransfer device to operate in a variety of countries with little or nomodification.

Embodiments of the robotic sample transfer device may include a humiditysensor disposed within the processing chamber of the device incommunication with the controller which is configured to sense thehumidity within the processing chamber. For some of these embodiments, aclosed loop feedback of sensed humidity levels within the processingchamber may be used in conjunction with a humidity control device formaintaining a substantially constant humidity within the processingchamber.

Embodiments of the robotic sample transfer device may include atemperature sensor disposed within the processing chamber of the sampletransfer device in communication with the controller which is configuredto sense the temperature within the processing chamber. For some ofthese embodiments, a closed loop feedback of sensed temperature levelswithin the processing chamber may be used in conjunction with atemperature control device for maintaining a substantially constanttemperature within the processing chamber.

A graphic user interface may be disposed on an outer surface of thehousing or in another convenient location and in communication with thecontroller. Some embodiments of the robotic sample transfer device mayinclude an imaging camera which may be coupled to an image processingcontroller, a bar code reader head and bar code reader processor incommunication with the bar code reading head and controller.

The fluid rinse station may include an array of regularly spacedindividual rinse tubes having a regular spacing corresponding to theregular spacing of the pin tools of the pin tool head assembly. A rinsefluid supply tank may be disposed within the housing and in fluidcommunication with the fluid rinse station. Some embodiments of thesample transfer device may include a rinse fluid supply pump disposedwithin the housing, in fluid communication with the rinse fluid supplytank and fluid rinse station and configured to pump rinse fluid from therinse fluid supply tank to the fluid rinse station. Some embodiments ofthe sample transfer device include a rinse fluid supply tank fluid levelindicator. Such an indicator may be used to provide users withinformation with regard to the fluid level within the rinse fluid supplytank so the tank may be refilled prior to running out of rinse fluid.

A waste fluid tank may be disposed within the housing in fluidcommunication with an overflow basin of the fluid rinse station. Someembodiments of the sample transfer device may include a waste fluid tankfluid level indicator. Such an indicator may be used to provide userswith information with regard to the waste fluid level within the wastefluid supply tank so the tank may be emptied prior to overflowing withwaste fluid.

An ultrasonic cleaning fluid reservoir may be disposed within thehousing in fluid communication with the self-leveling ultrasoniccleaning well. For some embodiments, the ultrasonic cleaning fluidreservoir includes a gravity feed reservoir having a supply portconfigured to couple into fluid communication with an inlet port of theultrasonic cleaning well. The supply port may be configured to allowfluid flow when coupled to the inlet port of the ultrasonic cleaningwell and be substantially sealed when the removed from the inlet port ofthe ultrasonic cleaning well.

A vacuum source may be disposed within the housing in fluidcommunication with the vacuum drying station. Some embodiments of thesample transfer device may also include a vacuum drying supply tank influid communication with the vacuum drying ports of the vacuum dryingstation. The vacuum drying supply tank may be a gas tight pressurevessel having an interior volume that may be partially emptied of air soas to provide a large volume of low pressure which can be used to drawair through the vacuum tubes of the vacuum drying station. Some of theseembodiments may include a vacuum pump in fluid communication with thevacuum drying supply tank.

FIGS. 1-14 illustrate an embodiment of an integrated robotic sampletransfer device 10 that may have features, dimensions and materialswhich are similar to or the same as the features, dimensions andmaterials of the robotic sample transfer device embodiments discussedabove. The integrated robotic sample transfer device 10 may be used forreliably transferring large numbers of samples from one position on awork surface of the device to second position on the work surface of thedevice. The integrated robotic sample transfer device embodiment 10shown includes a compact and user friendly configuration in that it doesnot require any external tanks or other major peripheral equipment inorder to operate. The ultrasonic wash station, rinse station and vacuumdrying station are all supplied by tanks that are disposed within thehousing of the transfer device. In addition, any waste fluid generatedby these stations drains to a waste fluid tank also disposed within thehousing. Although the wash fluid and waste tanks include coupling portsto allow a user to connect the tanks to larger external tanks ifdesired, having these primary wash fluid supply and waste tanks disposedwithin the housing allows a user having minimum work space toefficiently and effectively use the sample transfer device.

The transfer device 10 includes a housing 12 having an outer sheathingthat provides an enclosed processing chamber 14 that may be accessed bya hinged lid or door 16. The door may include a window with transparentsheathing material to allow a user to view the processes taking placewithin the processing chamber 14 while keeping the processing chamberenclosed and substantially isolated from the outside environment. Thetransparent sheathing of the window of the door 16 may include materialssuch as acrylic, PVC, polycarbonate and the like and have a thickness ofabout 0.1 inches to about 0.4 inches, for some embodiments. Such aconfiguration may allow the transparent material of the door 16 to besomewhat flexible and take on a curved shape or configuration. A safetyinterlock device (not shown) may include an interlock switch that iscoupled between the door 16 and the remainder of the housing 12. Theinterlock device may be configured to detect when the door 16 is open orclosed in order to prevent operation of the device 10, and particularlya robotic positioning system 18 of the device, while the door 16 isopen. The sheathing or skin of the housing 12 may be formed frommultiple panels of thin materials such as polymers, composites, metals,such as aluminum, and the like and may be secured to a frame structureof the housing 12. For some embodiments, the side panels of the housing12 may be removable in order to provide greater access to the processingchamber 14 during the loading and unloading of samples or devices fromwithin the processing chamber 14. An air port (not shown) may also bedisposed on one or more of the panels, such as the side panels, of thehousing 12 in order to provide an access port into the interior of thehousing 12 and processing chamber 14. Such an air port may be used toforce conditioned air into the processing chamber in order to controlthe temperature and humidity within the processing chamber 14.

The processing chamber 14 may be sized adequately to house the threeaxis robotic positioning system, work surface 22 and functional elementsof the work surface 22. In addition, it may be desirable to have accessby a user to some or all of these components in order to facilitateloading and unloading of samples, microtiter plates, chips, cleaningfluids and the like. The outer shape of the housing 12 is generallyrectangular, with a sloping front surface formed by the door 16 that ishinged across the top edge of the door 16 which is configured to swingup and down. One or more pressurized gas damping pistons 24 maypivotally secured between the door 16 and a portion of the housing 12beneath the door. The damping pistons 24 may be configured to offset theweight of the door 16 and provide damping of movement between the door16 and the remainder of the housing 12 to prevent rapid movement of thedoor 16 and keep the door 16 open until manually closed by a user. Someembodiments of the housing 12 may have a height of about 12 inches toabout 30 inches, more specifically, about 20 inches to about 26 inches,a width of about 20 inches to about 40 inches, more specifically, about25 inches to about 30 inches, and a depth of about 12 inches to about 30inches, more specifically, about 20 inches to about 26 inches.

A graphic user interface 26 that includes a touch screen user interfaceis disposed on an outside surface of the housing 12. The touch screenuser interface 26 may be a graphic screen coupled to a controller 28which is shown in FIG. 2. The touch screen user interface 26 allows auser to turn on, program, turn off and generally interact with thecontroller 28 and other features of the device through a menu driveninterface that is displayed on the touch screen. The controller 28 maybe used or programmed generally to control the use, motion or both ofthe active components of the sample transfer device 10. In particular,the controller may be used or otherwise programmed to control the use ofthe functional elements and supporting element or components of thefunctional elements of the work surface 22. For example, the controller28 may be used or otherwise programmed to control the movement offluids, such as rinse water supply and waste, pressurized gases, vacuumsources, such as drying vacuum sources, and the administration ofcleaning energy, such as ultrasonic cleaning energy for cleaning the pintools of a pin tool head assembly and the like. The controller 28 may beused to control the movement of the translatable carriers of the threeaxis robotic positioning system 18 and the use and control of imagingdevices secured to or otherwise associated with the translatablecarriers, such as imaging cameras, bar code readers and the like. FIG. 2is a rear elevation view of the sample transfer device embodiment 10with a rear panel of the housing 12 not shown for purposes ofillustration. With the rear panel of the housing removed, the controller28 and some of the associated electronics thereof are visible.

The controller 28 may include a processor 32, such as a computerprocessor, a memory storage unit and suitable accompanying circuitrysuch as logic circuits and the like. Some embodiments include auniversal power supply 34 coupled to the controller 28 and otherelectrical components of the sample transfer device that is configuredto supply a substantially constant operating voltage to the controller28 and other electrical components of the device for a variety of inputvoltages. Such a universal power supply 34 allows embodiments of therobotic sample transfer device 10 to be used with a variety of inputpower supply voltages without the need for modification. A customizedPCB board 36 that includes signal routing switches, motor controllers,an amplifier for ultrasonic energy generation, as well as othercomponents is mounted adjacent the processor 32. A cooling fan 38 isdisposed between the PCB board 36 and processor 32 for cooling theportion of the housing 12 that houses the controller 28.

The touch screen feature 26 allows a user to interact and make menuselections directly on the touch screen 26. For the embodiment shown,the touch screen user interface 26 is disposed on a hinged cover or doorthat is disposed over the front of a lower storage tank chamber 44 whichis shown in FIG. 3. The lower storage tank chamber 44 is a volumedisposed within the housing below a work surface 22 of the sampletransfer device 10. FIG. 3 shows a front elevation view of the sampletransfer device 10 with the hinged cover 42 of the lower storage tankchamber 44 removed for purposes of illustration.

FIG. 4 illustrates an enlarged perspective view of some of the activeprocessing components disposed within the processing chamber 14 of thesample transfer device embodiment 10. These active processing componentsare shown in an isolated view without the housing or other componentsfor clarity. Generally, the work surface 22 and functional elementsdisposed on the work surface 22 provide locations to secure samples andother materials in a first registered position so that they can be movedor moved in part to a second registered position, for example, moving aportion of a sample fluid from a known well of a microtiter plate to asample deposition site of a spectrometry chip with a pin tool. The threeaxis robotic positioning system 18 provides the system for generatingprecise motion relative to the registered positions of the work surface22, such as by providing precise known motion and positioning of a pintool relative to the work surface 22 and functional elements thereof.The work surface 22 and functional elements may also provide thenecessary tools to clean the pin tool or other transfer devices suchthat they may be used for many consecutive transfer cycles.

FIGS. 5 and 6 illustrate components of the three axis roboticpositioning system 18 in more detail. As shown, the three axis roboticpositioning system 18 is disposed substantially above the work surface22 and includes a fixed mount portion 46 which is secured in a fixedrelation with the work surface 22. Both the fixed mount portion 46 andthe horizontal work surface 22 may be secured in fixed relation to eachother on a frame structure 48 which may, in turn, be secured to orotherwise mounted to the housing 12 or frame structure of the housing12. For the embodiment shown, the frame structure 48 of the work surface22 and three axis robotic positioning system 18 is mounted to thehousing 12 with vibration isolating rubber mounts 52. Also for theembodiment shown, a base portion of the x-axis rail 54 serves as thefixed mount portion 46 of the three axis robotic positioning system 18.

The three axis robotic positioning system 18 includes a z-axistranslatable carrier 56 which is disposed above the work surface 22 andwhich may be controllably positioned in three different axes relative tothe work surface 22. The z-axis translatable carrier 56 is coupled tothe fixed mount portion 46 of the system or base of the x-axis rail 54through two other translatable carriers that provide the x-axis andy-axis components of the three axis motion. The three axes oftranslation of the translatable carrier of the three axis positioningsystem shown are substantially orthogonal to each other, however, someembodiments may use non-orthogonal axes. The z-axis translatable carrier56 may be translated in either direction along each of the three axesindependently. The movement of the translatable carrier in eitherdirection along each axis may be actuated by a stepper motor actuatorwhich is configured to impart linear motion along the direction of eachrespective axis.

Position information regarding the position of the translatable carrieralong one or more of the three axes may be measured by a linear encoderassembly, such as an optical linear encoder assembly, corresponding toone or more of the axes or by any other suitable method. A linearencoder assembly may include a linear encoder reader head such as anoptical linear encoder reader head and a linear encoder strip such as anoptical linear encoder strip that are coupled to the controller and mayprovide position feedback to the controller. A homing switch system mayalso be used to facilitate the determination of position of thetranslatable carriers along each of their respective axes. Such a homingswitch may be mounted at or near an end of the length of travel ormotion of a respective translatable carrier such that the homing switchis activated to open or close an electrical loop, optical loop or thelike as the translatable carrier reaches the end of travel at apre-determined and repeatable position. The electrical or optical loopof the homing switch may be coupled to the controller 28 such that thecontroller 28 may be programmed to move a translatable carrier to the“home” position which mechanically activates the homing switch at thebeginning of a transfer cycle or at any other desired time. For someembodiments, the controller 28 may home one or more of the translatablecarriers by sending a home command to one or more motor controllerscorresponding to each of the respective stepper motors. Such motorcontrollers may be located on board 36 or in any other suitablelocation. Once the home position has been determined, the controller 28may use the stepper function of the stepper motor actuator to track thenumber of motion pulses in each direction along the axes in order tocalculate or otherwise track the position along each of the axes.

The x-axis rail 54 of the three axis robotic positioning system 18extends across the processing chamber 14 and is coupled to an x-axiscarrier 58 which is coupled to a y-axis carrier 62 which is coupled tothe z-axis carrier. The x-axis carrier is configured to translate on thex-axis rail, the y-axis carrier 62 is configured to translate relativeto the x-axis carrier in a y-axis direction and the z-axis carrier isconfigured to translate in a z-axis direction relative to the y-axiscarrier 62. All three of the carriers and corresponding carrier railsupon which the carriers move may be respectively coupled together byhigh precision bearings that are configured to promote low frictionlinear movement with high precision. The z-axis carrier 56 may bepositioned in three axes which are substantially orthogonal to eachother for such a configuration. The pin tool head assembly 64 is securedto the z-axis carrier 56 and may also be positioned in the threesubstantially orthogonal axes. Various embodiments of the rails of thethree axis robotic positioning system 18 may include models SR20, RSR12Wand HSR20, manufactured by THK Company, Japan.

As discussed above, the z-axis translatable carrier 56 is translatablein the x, y and z axes and is coupled to the fixed mount portion 46 (orbase of the x-axis rail) through the y-axis translatable carrier 62 andthe x-axis translatable carrier with each translatable carrierconfigured to move independently of the other carriers in its respectivedirection. The pin tool head assembly 64 is secured directly to thez-axis translatable carrier 56 which moves up and down on the z-axisrail 66 relative to the y-axis translatable carrier 62 and horizontalwork surface 22. The y-axis translatable carrier 62 moves in a y-axisdirection front to back on a y-axis track relative to the x-axistranslatable carrier 58 and the horizontal work surface 22. The x-axistranslatable carrier 58 moves in an x-axis direction side to siderelative to the fixed mount portion 46 on the x-axis rail 54. Thesuperposition of movement in each of the x-axis, y-axis and z-axisdirections allows the z-axis translatable carrier 56 and pin tool headassembly 64 secured directly thereto to be positioned in threedimensions with respect to the horizontal work surface 22 and functionalcomponents disposed on the work surface 22. There may be no need formovement in a rotational orientation as the pin tools 68 of the pin toolhead assembly 64 are generally applied at a right angle or perpendicularto nominal upper surfaces of the functional components of the worksurface 22. However, an additional axis or axes of motion could be addedto the robotic positioning system 18. In addition, although the baseportion of the x-axis rail 54 serves as the fixed mount portion 46 andthe z-axis translatable carrier 56 serves as a three axis translatablecarrier, the various carriers may be mixed and matched as desired inorder to achieve the three axes of movement. For example, a base portionof a rail of either the x, y or z axis of a robotic positioning systemcould serve as the fixed mount portion 46 that is mounted in fixedrelation to the work surface 22. Also, either the x, y or z translatablecarrier may serve as the three axis translatable carrier of a roboticpositioning system 18, so long as the three axis translatable carrier iscoupled to the fixed mount portion through translatable carriers of theother two axes.

Referring to FIG. 5, the x-axis rail assembly 70 includes a frame 72that includes a bottom portion which is secured in fixed relation to theframe structure 48 beneath the rail assembly 70. The work surface 22 isalso secured in fixed relation to the same frame structure 48. As such,the bottom of the x-axis rail assembly 70 serves as the fixed mountportion 46 of the three axis robotic positioning system 18. The x-axisrail assembly 70 includes a first x-axis rail 74 upon which bearing cars76 are slidingly engaged and free to translate along the x-axisdirection. The x-axis rail assembly 70 includes a second x-axis rail 78upon which a bearing car 76 is slidingly engaged and free to translatealong the x-axis direction. The x-axis translatable carrier 58 issecured to the bearing cars of the x-axis rail assembly 70 and thus thex-axis translatable carrier 58 is free to move along the x-axisdirection riding on the multiple bearing cars 76. A threaded rod 82 issecured between end plates 84 and 85 of the x-axis rail assembly 70.X-axis stepper motor 86 has a threaded collar 88 that is in threadedengagement with the threaded rod 82. The threaded collar 88 isconfigured to rotate with a rotor of the stepper motor 86 but remainstable in an axial direction relative to the stepper motor body. Thestepper motor 86 thus moves along and relative to the threaded rod 82,frame 70 and x-axis when the stepper motor 86 drives the threaded collar88 which rotates relative to the threaded rod 82. The x-axis steppermotor 86 is also secured in fixed relation to the x-axis translatablecarrier 58 and thus drives the x-axis translatable carrier 58 along thex-axis direction when actuated. For such an arrangement, the threadedcollar 88 of the stepper motor 86 may include an anti-backlash device inorder to maintain high precision linear movement of the x-axistranslatable carrier 58. An linear encoder strip 92 is disposed on afront surface of the rail assembly 70 as shown in FIG. 4, which may beread by an encoder head 94 which is secured to the x-axis translatablecarrier as shown in FIG. 3. The linear encoder strip 92 may includemodel RGS40S, manufactured by Renishaw Corporation located inGloucestershire, England. The linear encoder reader head 94 may includemodel RGH41, also manufactured by Renishaw Corporation. The linearencoder systems may have a resolution of about 0.5 microns to about 5microns, more specifically, about 0.8 microns to about 1.5 microns, forsome embodiments. The various stepper motor embodiments may includemodel series 57000, size 23, and model series 43000, size 17,manufactured by Hayden Switch and Instrument Company, Waterbury, Conn.

Referring to FIG. 4, a y-axis rail assembly 96 is secured to the x-axistranslatable carrier 58. The y-axis rail assembly 96 includes a frame 95y-axis rail 98 upon which a bearing car (not shown) is slidingly engagedand free to move along the y-axis direction. The y-axis translatablecarrier 62 is secured to the bearing car of the y-axis rail assembly 96and thus the y-axis translatable carrier 62 is free to move along they-axis direction riding on the bearing car. A threaded rod 102 issecured between end plates 104 and 105 of the y-axis rail assembly 96.Y-axis stepper motor 106 has a threaded collar 108 that is in threadedengagement with the threaded rod 102. The threaded collar 108 isconfigured to rotate with a rotor of the stepper motor 106 but remainstable in an axial direction relative to the stepper motor body. Thestepper motor 106 thus moves along and relative to the threaded rod 102,frame 95 and y-axis when the stepper motor drives the threaded collar108 which rotates relative to the threaded rod 102. As with the x-axisassembly 70, the threaded collar 108 of the stepper motor 106 mayinclude an anti-backlash device in order to maintain high precisionlinear movement of the y-axis translatable carrier 62. A y-axis linearencoder strip 112 is disposed along a top portion of the y-axis railassembly 96. A y-axis linear encoder reader head (not shown) may bedisposed on the y-axis translatable carrier 62 and configured to readthe y-axis linear encoder strip 112. The encoder strip 112 and readerhead may be the same as or similar to the x-axis encoder strip 92 andreader head 94 discussed above.

A z-axis rail assembly 114 is secured to the y-axis translatable carrier62 to provide controllable high precision movement along the z-axisdirection in combination with x-axis and y-axis movement provided by therespective translatable carriers 58 and 56 in those axes. The z-axisrail assembly 114 includes a z-axis rail 116 upon which one or morebearing cars (not shown) are slidingly engaged and free to translatealong the z-axis direction with high precision. The z-axis translatablecarrier 56 is secured to the bearing car of the z-axis rail assembly 114and thus the z-axis translatable carrier 56 is free to move along thez-axis direction riding on the bearing cars. A threaded rod 118 issecured to the z-axis translatable carrier. Z-axis stepper motor 122 issecured to the y-axis translatable carrier 62 by a mount bracket 124 andincludes a threaded collar 126 that is in threaded engagement with thethreaded rod 118. Thus, when the z-axis stepper motor 122 is actuatedand the threaded collar 126 rotated, the threaded rod 118 and z-axistranslatable carrier 56 is moved along z-axis relative to the y-axistranslatable carrier 62. As with the x-axis and y-axis assemblies, thethreaded collar 126 of the stepper motor 122 may include ananti-backlash device 56 in order to maintain high precision linearmovement of the z-axis translatable carrier 56.

The positioning of the z-axis translatable carrier 56 along the z-axisdirection may be determined by the use of a homing switch as discussedabove. For the embodiment shown, a homing switch 128 is disposed infixed relation to the y-axis translatable carrier 62 near the top end ofthe z-axis motion of the z-axis carrier 56 such that the z-axis carrier56 activates the homing switch 128 at the top of the z-axis travel. Thehoming switch 128 is coupled to the controller 28 which may then “home”the z-axis translatable carrier 56 at the beginning of each sampletransfer cycle, or at any other desired time, in order to determine theposition of the z-axis translatable carrier 56 thereafter. Such a homingposition determination process may also be manually selected by a user.The z-axis rail assembly 114 may also optionally include a linearencoder assembly, such as the linear encoder assemblies discussed abovewith regard to the x-axis rail assembly 70 and y-axis rail assembly 96,if greater precision is desired for the determination of the position ofthe z-axis translatable carrier 56.

The x-axis rail 54 and translatable carrier 58 may be configured toprovide about 10 inches to about 30 inches of travel in the x-axisdirection, more specifically, about 20 inches to about 25 inches oftravel in the x-axis direction. The y-axis rail 98 and translatablecarrier 62 may be configured to provide about 8 inches to about 16inches of travel in the y-axis direction, more specifically, about 10inches to about 12 inches of travel in the y-axis direction. The z-axisrail 116 and translatable carrier 56 may be configured to provide about2 inches to about 10 inches of travel in the z-axis direction, morespecifically, about 3 inches to about 5 inches of travel in the z-axisdirection.

As shown in FIG. 6, an imaging camera 132 is secured to the y-axistranslatable carrier 62. The imaging camera 132 may be configured tohave a focal length or range of focus that matches the distance from theimaging camera 132 to a plane below the camera 132 that is substantiallyat the level or plane of nominal upper surfaces of the functionalelements of the work surface 22. For some embodiments, the work surface22 may be configured such that some or all of the functional componentsthereof have a nominal upper surface that is at substantially the samez-axis level or position. This configuration may serve to simplify theprogramming of the controller 28 for sample transfer procedures. Thisconfiguration may also allow the imaging camera 132 in a fixed z-axisposition to remain in focus while imaging a nominal upper surface of thefunctional components in order to better control the sample transferprocess. A bar coder reader head 134, as shown in FIG. 2, may alsosecured to the y-axis translatable carrier 62, y-axis rail 98 or anyother suitable portion of the robotic positioning system 10. The samearrangement may be desirable for easy scanning of bar codes disposed onchips, microtiter plates or the like that are placed on mount blocks ofthe work surface 22 for easy identification and obtaining accurateposition data of such components. The bar code reader head 134 mayinclude model NLV-1001, manufactured by Opticon Corporation, Japan.

Referring to FIG. 6, the pin tool head assembly 64 is secured to thez-axis translatable carrier 56 by fasteners such as screws or bolts andis movable and may be positioned in all three x, y and z axes. The pintool head assembly 64 includes a substantially rigid frame structure 136having a first vertical support plate 137 and a second vertical supportplate 138 spaced laterally from the first vertical support plate 137 anddisposed substantially parallel to the first vertical support plate 137.A bottom plate 139 is secured at a first end to the first verticalsupport plate 137 and secured at a second end to the second verticalsupport plate 138. The bottom plate 139 has a top surface and a bottomsurface that is substantially parallel to the top surface. The bottomplate 139 may have a thickness of about 0.05 inches to about 0.5 inches,more specifically, about 0.1 inches to about 0.2 inches, for someembodiments. The bottom plate 139 may be oriented substantiallyperpendicular to both the first and second vertical support plates 137and 138. A cover plate 140 is disposed opposite and spaced verticallyfrom the bottom plate 139. The cover plate 140 is secured to topsurfaces of upper ends of the first and second vertical support plates137 and 138 in an orientation that is substantially perpendicular toboth the first and second vertical support plates. The cover plate 140may have a thickness of about 0.05 inches to about 0.5 inches, morespecifically, about 0.1 inches to about 0.2 inches, for someembodiments. An open cavity or window is formed in the middle of therigid frame 136 between the upper surface of the bottom plate 139, alower surface of the cover plate 140, and interior surfaces of both thefirst and second vertical support plates 137 and 138.

An array of pin tools 68 is mounted on the bottom plate 139 and coverplate 140 with a configuration that allows axial translation of the pintools 68 relative to the frame structure 136 in an upward direction. Thepin tools 68 have an elongate shaft 142, a nominal shaft portion and anenlarged portion of the shaft 142 that may include an enlarged portion143 in the form of a collar member 144 to stop axial movement of the pintool shaft 142 against either the bottom plate 137 or cover plate 140 ofthe frame structure 136. For the embodiment shown, the pin tools 68 aredisposed in a 4 by 6 pin array with spacing or pitch between adjacentpin tools of about 3 mm to about 10 mm, more specifically, about 4 mm toabout 5 mm. The pin tools 68 are disposed in close fitting holes in thebottom plate 139 that have an inside diameter or transverse dimensionthat corresponds to an outer transverse dimension or diameter of thenominal shaft portion of the elongate shaft 142 of each respective pintool 68. The amount of clearance between an outer surface of each pintool 68 and an insider surface of the respective hole in the bottomplate may be about 0.0002 inches to about 0.001 inches. Each pin tool 68is also disposed in a mating hole or slot in the cover plate 140 whichmay have similar clearance and may provide additional longitudinalstability for axial movement of the pin tool shaft 142 within the framestructure 136.

Either or both of the pin tool shaft holes or slots in the bottom plate139 or cover plate 140 may have a keyed configuration that matches akeyed configuration of an outside surface of the pin tool shaft 142 soas to prevent rotation of the pin tool shafts 142 relative to the framestructure 136, but allow unimpeded axial movement of the pin tool shafts142 relative to the frame structure 136. A top portion 146 of the pintool shafts 142 shown have a “D” shaped transverse cross section whichmates with a respective “D” shaped hole in the cover plate 140. Althoughthe pin tool head assembly 64 embodiment shown has a 4 by 6 pin toolarray, other configurations are also contemplated. For example, somearrays of pin tools 68 of a pin tool head assembly 64 may have a row ofabout 1 pin tool to about 15 pin tools in conjunction with columns ofabout 2 pin tools to about 30 pin tools, for some embodiments. Someembodiments may have a row of about 3 pin tools to about 10 pin tools inconjunction with columns of about 2 pin tools to about 15 pin tools.

For some embodiments, an enlarged portion 143 of the pin tool shaft 142may be integrally formed into the shaft 142. For the pin toolembodiments shown, an enlarged portion 143 of the elongate shaft 142 ofthe pin tools 68 is formed by the separate collar member 144 which maybe secured to the elongate shaft 142 by a variety of suitable methodssuch as a compression fit, adhesive, solder or the like. The collarmembers 144 shown are clips that are secured by compression fit intocircumferential slots or grooves 148 formed into the shafts 142 of thepin tools 68. As the collar member 144 is larger than the pin tool shaftholes in the bottom plate, the enlarged portion or collar member 144comes to a hard stop against the upper surface of the bottom plate 139at the end of downward axial translation of the pin tool shaft 142. Theenlarged portion 143 of the elongate shafts 142 of the pin tools 68 maybe biased in an axial direction against the bottom plate 139 of theframe structure 136 by gravity, a resilient bias member, such as ahelical spring 152, or by any other suitable device or method. For theembodiment shown, each pin tool 68 is biased against the bottom plate139 by a helical spring 152 which is disposed over each elongate shaft142 between the lower surface of the cover plate 140 and an uppersurface of the collar member 142 of each pin tool. A washer or bushingmay be disposed adjacent the collar members 144 between the collarmember 144 and spring 152 to provide a uniform surface for the spring152 to push against. The helical spring 152 may have a length in arelaxed uncompressed state that is longer than the distance between theupper surface of the bottom plate 139 and lower surface of the coverplate 140 so as to provide continuous resilient bias against upwardaxial translation of the pin tool 68. The bias against upward axialtranslation may also increase as the spring member 152 becomescompressed.

For some embodiments, the pin tool shafts 142 may have a length of about1 inch to about 4 inches, more specifically, about 2 inches to about 3inches. The elongate shafts 142 of the pin tools 68 may have an outertransverse dimension or diameter of about 0.03 inches to about 0.1inches, more specifically, about 0.05 inches to about 0.07 inches, forsome embodiments.

Sample reservoirs 156 may be disposed in distal ends or portions 158 ofthe elongate shafts 142 of the pin tools 68, distal of the enlargedportion 143 of the shaft 142 such which may include the collar member144. The collar member 144 is disposed and mechanically captured in thewindow of the frame structure 136 with the distal end 158 of the pintool shafts 142 extending below the pin tool shaft holes in the bottomplate 139. In this way, the distal ends 158 and sample reservoirs 156 ofthe pin tools 68 extend below the bottom plate 139 and may be used toaccess samples, such as arrays of samples disposed in vessels such asmicrotiter plates. The distal ends and sample reservoirs 156 of the pintools 68 may also be used to access sample deposition sites, such asarrays of sample deposition sites disposed on a spectrometry chip. Forsome embodiments, the width of a slot 162 of the sample reservoir of thepin tools may be sized to be greater than an outer lateral transversedimension of a matrix deposit of a sample deposition site of aspectrometry chip. In this way, a sample from the sample reservoir ofthe pin tool may be deposited onto the matrix deposit of the chipwithout the pin tool structure making contact with the matrix material.In other words, the slot of the sample reservoir may be configured tostraddle the matrix material of the sample deposition site.

Some embodiments of the sample reservoir 156 may include a thin slot 162having a width of about 0.2 mm to about 0.5 mm, more specifically, about0.25 mm to about 0.4 mm, and may have a length of about 0.1 inches toabout 0.5 inches, more specifically, about 0.18 inches to about 0.22inches, depending on the desired amount of liquid volume to bedelivered. The frame structure 136 and pin tools 68 may be configured,particularly with regard to the placement of the collar member 144relative to the distal end 158 of the pin tools 68, such that the distalends 158 of the pin tools 68 of a pin tool array are coplanar and alllie substantially in a plane that is substantially parallel to the worksurface 22. Each pin tool 68 of the array may also be substantiallyperpendicular to the work surface 22.

The work surface 22 is generally configured to be disposed in asubstantially horizontal orientation and may include one or morefunctional elements disposed thereon. Because some of the functionalelements of the work surface 22 may include fluids disposed inenclosures, the substantially horizontal orientation of the work surface22 may serve to prevent spillage of the fluids and provide moreconsistent operation and sample transfer generally. FIG. 7 shows anenlarged perspective view of a work surface embodiment 22 and functionalelements disposed thereon. FIGS. 8-11 show additional views and detailsof the work surface 22 and functional element embodiments associatedtherewith.

The controller 28 as well as other electronics that control the movementof the pin tool head assembly 64 (that may include a controller with aprocessor and other sensitive electronic components) as well as controland operation of other components of the transfer device 10 may bedisposed above the level of the work surface 22 of the transfer device.With such a configuration, any accidental spills of fluid that occur onthe work surface 22 will not compromise the integrity of suchelectronics.

For the embodiment shown, the work surface 22 is disposed beneath thethree axis translatable carrier 56 of the three axis robotic positioningassembly 18 and includes a substantially flat rectangular surface of arectangular plate upon which the functional elements may be directly orindirectly secured or otherwise mounted. For some embodiments, the worksurface 22 itself may be formed from one or more upper nominal surfacesof one or more functional elements discussed herein without theinclusion of a separate flat rectangular surface or plate. For someembodiments, the rectangular plate of the work surface 22 may have awidth of about 4 inches to about 16 inches, more specifically, about 5inches to about 10 inches and may have a length of about 10 inches toabout 30 inches, more specifically, about 15 inches to about 20 inches.The plate of the work surface 22 may be secured to frame members 48which may in turn be secured to the frame of the housing 12 or otherstructural members of the sample transfer device 10 with solid mounts orvibration absorbing mounts 52 such as the rubber mounts shown.

Referring to FIG. 7, a cleaning block assembly 164 is disposed on andsecured to the work surface plate. The cleaning block assembly 164 mayhave one or more functional elements which are configured to clean eachpin tool of a pin tool 68 array of a pin tool head assembly 64simultaneously. The cleaning block assembly embodiment 164 may bemachined from a monolithic block of a strong stable material, such aspolymers, such as Delrin®, composites and metals, such as stainlesssteel, aluminum, which may be anodized, and the like. The cleaning blockassembly 164 may include functional elements in the form of aself-filling ultrasonic wash station 166 that is self-filled by agravity feed supply reservoir 168, pin tool wash or rinse station 172that includes an array of regularly spaced rinse tubes or fountains 174that may correspond to each pin tool 68 of the pin tool head assembly64. The rinse station 172 is disposed between the ultrasonic washstation 166 and a vacuum drying station 176.

The vacuum drying station 176 includes an array of regularly spacedvacuum drying orifices 178 that may correspond to each pin tool of thepin tool 68 head assembly 64. Although not necessary, it may bedesirable for the rinse station 172 and vacuum drying station 176 tohave an array of rinse tubes 174 or vacuum ports or orifices 178 with aregular spacing that corresponds to the regular spacing of the pin toolarray of a pin tool head assembly 64 to be used with these stations andan array size at least as big as the array of pin tools 68 of the pintool head assembly 64. Even though it may be acceptable for some pintools 68 of an array which are laterally displaced from a functionalelement of the cleaning block 164 to press against a surface adjacent arinse tube 174 or vacuum orifice 178, it may be desirable for all pintools 68 of an array to be cleaned simultaneously. As such, it may alsobe desirable for an ultrasonic bath 182 to have inner transversedimensions that are greater than corresponding outer transversedimensions of an array of pin tools to be washed in the ultrasonic washstation 166. It may also be desirable for the rinse station 172 andvacuum drying station 176 to have at least as many rinse tubes 174 andvacuum drying orifices 178 as there are pin tools 68 in a pin tool headassembly 64 to be cleaned.

In general, a pin tool array that has been used for transferringsamples, such as liquid samples, may then be moved over the work surface22 so as to align the array with the ultrasonic bath 182 of theultrasonic wash station 166. The sample reservoirs 156 and distalsections 158 of the pin tools 68 generally, may then be lowered into theultrasonic bath 182 such that any portion of the pin tools 68 that havebeen exposed to sample material, will be submerged in the ultrasonicbath 182. An ultrasonic actuator 184 disposed below the ultrasonic bath182 and cleaning block 164 may be activated to as to emit ultrasonicenergy into the bath 182 and promote cleaning and rinsing of each pintool 68 of the array. The pin tools 68 may be soaked in the ultrasonicbath 182 with ultrasonic energy agitating the water and surface of thepin tool 68 for about 1 second to about 2 minutes, more specifically,about 5 seconds to about 30 seconds, for some process embodiments. Theultrasonic energy emitted into the bath 182 may have a power of about 10watts to about 100 watts, more specifically, about 20 watts to about 40watts, and a frequency of about 20 kHz to about 60 kHz, morespecifically, about 30 kHz to about 50 kHz, and even more specifically,about 35 kHz to about 45 kHz. The ultrasonic wash fluid used in theultrasonic bath 182 may include de-ionized water, alcohol, and the likein a volume of about 10 ml to about 1000 ml, more specifically, about 20ml to about 100 ml.

Referring to FIGS. 7 and 10, an upper nominal surface 186 of theultrasonic wash bath 182 is disposed evenly with a nominal upper surface188 of the cleaning block assembly 164. The wash bath is disposed belowthe upper nominal surface 186 between side walls formed into thecleaning block and a top actuator surface 192 of an ultrasonic energygenerator or transducer 194. The ultrasonic energy generator 194interior volume 182 is disposed below the ultrasonic bath 182 andsecured thereto by multiple fasteners in a sealed arrangement such thatthe ultrasonic generator 194 is coupled directly to the wash fluidwithin the ultrasonic bath 182.

The ultrasonic wash bath 182 of the ultrasonic wash station 166 isself-filled by a self-leveling gravity feed system supplied by a washfluid reservoir 168. The wash fluid reservoir 168, as seen in FIG. 7A,may include a generally cylindrical bottle 196 having a ball valve 198that allows a user to refill the reservoir 168 and couple an outlet port202 of the reservoir to an inlet port 204 of the ultrasonic wash station166 without spilling a significant amount of the wash fluid. The washfluid reservoir 168 is shown tipped up with the outlet port of thereservoir 168 coupled into the inlet port 204 of the wash station 166.The inlet port 204 of the wash station 168 is in fluid communicationwith the ultrasonic wash bath 182 via a fluid tight conduit (not shown)that extends between the inlet 204 port and wash bath 182 underneath theupper nominal surface 188 of the cleaning block 164. The ball valve 198may include a spherical ball 206 made of an inert material such asViton® rubber or the like which is configured to seal against an insidelip of the reservoir bottle 196 and provide a seal. It may be importantfor the ball 206 of the ball valve 198 to have an overall density whichis greater than the density of the cleaning fluid to be used in thereservoir 168. As such, it may be desirable for the ball 206 to have adensity which is greater than water, ethanol alcohol, and other suitablecleaning fluids. The outlet port 202 of the wash fluid reservoir 168 mayinclude a cylindrically shaped portion 208 extending from a bottomsurface 212 of the reservoir 168. The cylindrically shaped portion 208may also have an o-ring or similarly configured resilient seal 214 thatmay seal between the cylindrically shaped portion 208 and an insidesurface 216 of the inlet port 204 of the ultrasonic wash station 166.The wash fluid reservoir 168 may have a capacity of about 20 ml to about1 liter, more specifically, about 40 ml to about 60 ml, for someembodiments.

After the ultrasonic wash bath fluid has been used one or more times,and the operator determines that the wash fluid needs to be changed, theused wash fluid may then be drained through a drain port 218 in theultrasonic wash bath 182 that is in communication with a flexible fluidtight tube that is coupled to an optional pump 222. When the pump 222 isactivated by the controller 28 or other user input, the fluid in theultrasonic wash 182 shown in FIGS. 2 and 12 may be actively drained fromthe wash bath 182 through the pump 222 and into a waste fluid tank 224which is disposed below the processing chamber 14 and shown in FIG. 2.The drainage of the wash bath 182 may also be controlled by a solenoidvalve or the like which may optionally be coupled to and controlled bythe controller 28.

Thus, the controller 28 may be programmed to drain the ultrasonic washbath 182 fluid after a predetermined number of uses. As the wash bath182 is being drained, new clean ultrasonic wash fluid begins to refillthe wash bath 182 by force of gravity from the wash fluid reservoir 168through the fluid tight conduit and into the wash bath 182. As the washbath 182 begins to fill, the back pressure on the outlet port 202 of thereservoir 168 increases until equilibrium is achieved within theinterior volume of the reservoir 168 and wash fluid ceases to flow fromthe reservoir 168 into the wash bath 182. When the wash fluid becomesdirty again after use, the cycle may be repeated until the reservoir 168runs out of wash fluid. As such, it may be desirable to construct thebottle 196 of the reservoir 168 from a transparent or translucentmaterial or materials that will make the fluid level within thereservoir 168 visible to a user of the sample transfer device 10. Thefluid reservoir 168 also serves to maintain the ultrasonic bath 182 at adesired pre-determined level during use and can be used to automaticallyadd additional cleaning fluid to replace cleaning fluid lost throughevaporation, adherence to pin tools 68 and pin tool sample reservoirs156 after a cleaning cycle or the like.

An optional overflow channel 226 is disposed around the inlet port 204of the wash fluid reservoir 168, the ultrasonic wash bath 182 and therinse tubes 174 of the rinse tube station 172. The overflow channel 226may serve to confine any spilled cleaning fluid to the channel 226 andallow the spilled cleaning fluid to drain down the rinse station drain228 by force of gravity. The overflow channel 226 may be cut into theupper nominal surface 188 of the cleaning block 164 to a depth of about0.05 inches to about 0.4 inches, more specifically, about 0.1 inches toabout 0.2 inches. A lip 232 of the upper nominal surface 188 of thecleaning block 164 surrounds the ultrasonic bath cavity 182 and formsthe upper nominal surface of the ultrasonic wash station 166.

The rinse station 172 includes a plurality of rinse tubes 174 arrangedwith a regular pre-determined spacing that may be configured to matchthe regular spacing of the pin tools 68 of a pin tool array to be usedwith the rinse station 182. The upper ends 234 of the rinse tubes 178may lie substantially in a plane disposed at substantially the samez-axis level. The upper ends 234 of the rinse tubes 174 may also be atsubstantially the same z-axis level as the nominal upper level 188 ofthe cleaning block 164 and form the nominal upper surface of the rinsetube station 172. The rinse tubes 174 may be elongate hollow tubeshaving an inner lumen 236 with an inner transverse dimension or diameterof about 0.05 inches to about 0.2 inches, more specifically, about 0.07inches to about 0.1 inches. The inner lumens 236 of the rinse tubes 174may be coupled by a manifold assembly to a fluid tight tube in fluidcommunication with a rinse pump 238 which is in turn in fluidcommunication with a wash fluid supply tank 242 shown in FIG. 3. Oncethe pin tool or pin tools 68 of a pin tool head assembly 64 are disposedwithin the rinse tubes 174, rinse fluid may then be expelled verticallyfrom the rinse tubes 174 to provide a continuous flow of rinse fluidover the sample reservoirs 156 and distal section 158 generally of thepin tools 68. The flow of rinse fluid may be maintained for about 1seconds to about 10 seconds, more specifically, about 3 seconds to about5 seconds, for some embodiments. The amount of flow of rinse fluidthrough each individual rinse tube 174 may be about 20 ml per minute toabout 100 ml per minute, more specifically, about 20 ml per minute toabout 30 ml per minute.

The rinse fluid may include de-ionized water, alcohol including ethanol,or any other suitable cleaning fluid. After the rinse fluid has beenexpelled from the rinse tubes 174, it flows by force of gravity over thesides of the rinse tubes 174, into the overflow channel 226 discussedabove and down the rinse station drain 228. The overflow channel 226surrounding the rinse tubes 174 may have a depth of about 0.2 inches toabout 1 inch, more specifically, about 0.3 inches to about 0.5 inches,for some embodiments. The rinse station drain 228 is a relatively largebore drain that is coupled to the waste fluid tank 224 by a flexibletubing. The bore of the rinse station drain 228 may have a transversedimension or diameter of about 0.2 inches to about 1 inch, morespecifically, about 0.3 inches to about 0.8 inches.

The vacuum drying station 176 includes a plurality of substantiallyparallel vertical holes 244 disposed in the cleaning block 164 arrangedin a regularly spaced array that may be configured to match the regularspacing of the pin tools 68 of a pin tool head assembly 64 to be driedby the vacuum drying station 176. The vertical holes 178 are formeddirectly into the material of the cleaning block 164 having upperapertures or orifices 178 that lie in substantially the same plane asthe upper nominal surface 246 of the vacuum drying station 176. Thevertical holes 244 may have an inner transverse dimension or diameterthat is larger or just slightly larger than an outer transversedimension or diameter of the pin tools 68 to be used in the vacuumdrying station 176. For some embodiments, the vertical holes 244 mayhave an inner transverse dimension or diameter of about 0.04 inches toabout 0.1 inches, more specifically, about 0.07 inches to about 0.1inches. The vertical holes 244 may have a depth of about 0.1 inches toabout 1 inch, more specifically about 0.3 inches to about 0.5 inches.

A bottom end or bottom orifice (not shown) of each vertical hole 244 maybe coupled to a manifold which is coupled to a vacuum holding tank 248,shown in FIG. 2, disposed below the work surface 22 in the lower chamber44 by a length of flexible tubing (not shown). The flexible tubing mayhave a wall thickness and mechanical integrity suitable for holding avacuum or partial vacuum for some embodiments. A valve, such as asolenoid valve (not shown), which may be coupled to and controlled bythe controller 28, may be coupled to the flexible tubing in fluidcommunication with the vacuum storage tank 248 and vertical holes 244 ina configuration that allows the application of stored vacuum in the tank248 to be applied to the vertical holes 244 when the pin tools 68 of apin tool head assembly 64 are disposed within the vertical holes 244. Ifthe vacuum storage tank 248 has been emptied of most of the air withinthe storage tank 248, air will be drawn through the vertical holes 244at a high rate of flow and through the flexible tubing when the solenoidvalve is opened in order to fill the vacuum within the vacuum storagetank 248. For some embodiments, the vacuum storage tank 248 may have aninterior volume of about 1 liter to about 3 liters, more specifically,about 1.5 liters to about 2 liters. For some embodiments, the vacuum maybe applied to the vertical holes 244 for drying pin tools 68 disposedtherein for about 0.1 seconds to about 0.8 seconds, more specifically,about 0.2 seconds to about 0.4 seconds.

A relieved slot or channel 252 may be formed into a front surface of thecleaning block 164 in front of the vacuum drying station 176. The slot252 may be configured to accept a rail feature 254 of a multi-wellcalibration material supply vessel 256 shown in FIG. 7C. The supplyvessel 256 may be detachably disposed into the slot 252 by sliding therail feature 254 of the supply vessel 256 vertically downward into theslot 252 until it hits a stop point. One or more calibration materialsmay be disposed in the individual wells 258 of the supply vessel and thesupply vessel 256 then placed in the slot 252 of the cleaning block 164.The controller 28 may be programmed to dip one or more pin tools 68 tobe used for calibration purposes into a pre-determined well of thesupply vessel 256 in order to draw in calibration material into thesample reservoir 156 of the pin tool 68 to be used for calibration. Oncethe calibration material runs out or gets low, or the user decides touse another type of calibration material, the supply vessel 256 may bemanually removed from the cleaning block 164 and replaced with anotherfull supply vessel 256. For some embodiments, the supply vessel 256 mayhave about 1 well to about 10 wells, more specifically, about 2 wells toabout 8 wells. FIG. 7D illustrates and embodiment of a supply vessel256′ having a single well 258′ and a rail feature 254′ that may also beconfigured to engage slot 252.

The slot 252 of the cleaning block 164 and rail feature 254 and 254′ ofthe supply vessel embodiments 256 and 256′ may be configured such thatrespective upper nominal surfaces 262 and 262′ of the supply vesselembodiments are disposed above the upper nominal surface 188 of thecleaning block 164 for some embodiments. This allows the pin tools 68 tobe used for calibration purposes to dip into the wells 258 of the supplyvessels without the remainder of the pin tools 68 making contact withadjacent cleaning block elements or structures. As such, the railfeature embodiments 254 and 254′ and slot 252 may be configured suchthat the height of the nominal surface 262 of the supply vessel 256 maybe disposed above the nominal upper surface 188 of the cleaning block164 by a distance that is at least the length of a pin tool 68 thatneeds to be inserted into the calibration material plus the distancebelow the upper nominal surface of the supply vessel embodiments of thecalibration material.

Some of the functional elements of the work surface 22 may be secured tothe plate by fasteners such as machine screws or the like and somefunctional elements, such as microtiter plates, chips and chip mountblocks may be releasably secured to the work surface, or mount blockdisposed thereon, with elements such as spring loaded toggles, clips,magnets or the like to allow the easy and convenient exchange of suchfunctional elements. Functional elements such as microtiter plates,chips and chip mount blocks may contain samples to be transferred orsample deposition sites that need to be changed as processing takesplace and progresses. The work surface shown in FIG. 7 includes twomicrotiter plate mount blocks 264 disposed adjacent a chip mount block266. The microtiter plate mount blocks 264 are configured to releasablysecure microtiter plates 268 having a uniform and standardizedconfiguration with an array of sample wells 270. This allows such astandardized microtiter plate 268 to be easily mounted and removed fromthe work surface 22 with some of the important aspects of the microtiterplate 268 (such as sample well location and upper nominal surfacelocation) disposed in a consistent position with respect to the worksurface 22.

The chip mount block 266 may also be releasably secured to a mountplatform 272 which is secured to the work surface 22 and configured toreleasably secure the chip mount block 266 thereto with spring loadedtoggles or the like. This allows the chip mount block 266 to bepreloaded with one or more chips, such as the spectrometry chip 274shown in FIGS. 11A and 11B, away from the work surface 22. The chipmount block 266 that has been preloaded with chips 274 may then bereleasably secured to the mount platform 272 on the work surface 22 bythe toggles 276. The mount platform 272 may be sized to have a thicknessor otherwise be configured to position an upper nominal surface 278 ofthe chip mount block 266 (and chips 274 mounted thereto for someembodiments) at a level which is even with upper nominal surfaces 188 ofthe cleaning block 164 and other functional elements disposed on thework surface 22.

The chip mount block 266 may have one or more chip mount sites 288 orwells which are configured to releasably secure one or more chips 274,such as mass spectrometry chips, having at least one array of sampledeposition sites disposed thereon. The chips 274 may be mounted to chipmount sites 282 the chip mount block 266 by gravity, friction, springloaded toggles, magnets and the like. The chip mount block 266 may alsosecure the chips 274 thereto by having each chip 274 disposed within acavity of the chip mount sites 282 formed in an upper surface of thechip mount block 266 which is sized to substantially conform to an outeredge of pre-selected embodiments of chips 274. Such cavities may be usedto partially mechanically capture the mounted chips 274 and preventlateral movement of the chips 274 relative to the chip mount block 266.For the embodiment shown, each chip mount cavity well 282 has a magneticsource, such as a ferrous magnet 284 disposed in a bottom surface of thechip mount well 282. Each chip 274 to be used for such an embodiment,may have a layer of ferrous metal, such as a disc 286 made of steel orthe like, secured to a rear surface 288 of the chip 274 as shown inFIGS. 11A and 11B. When such a chip embodiment 274 is placed in a chipmount well 282, the magnet 284 of the chip mount well 282 attracts thedisc 286 secured to the chip 274 and holds the chip 274 in the chipmount well 232. By having the magnet 284 of the chip mount well 282offset from the position of the ferrous metal disc 286, the chip 274 mayalso be pulled laterally into a corner of the chip mount well 282 inorder to register the position of the corner of the chip 274 to a knowncorner of the chip mount well 282 and provide a reliable positioning ofthe chip 274 within the chip mount well 282.

Referring to FIGS. 11A and 11B, each chip 274 may include one or morearrays of sample deposition sites 292 which are regularly spaced fromeach other at periodic intervals on a flat working surface 293 of thechip 274. Also, as discussed above, each chip 274 may have a ferrousmetal disc or layer 286 disposed on the rear surface 288 of the chip 274for releasable mounting purposes. For some embodiments, an array ofsample deposition sites 292 on a chip 274 may be configured as a squareorthogonal array of sample deposition sites 292 wherein each sampledeposition site 292 is disposed an equal distance away from the adjacentsample sites 292 along orthogonal axes that transect the sample sites292. Such an orthogonal array of sample sites 292 may have a spacingbetween adjacent sample sites of about 1 mm to about 3 mm, morespecifically, about 1.1 mm to about 1.4 mm. For some embodiments, a chip274 may include two, three or more arrays of sample deposition sites292, each array having a regular spacing of sample deposition sites 292.Each of the multiple arrays of sample deposition sites 292 may be squareorthogonal, linear or have any other desirable configuration. It mayalso be desirable for one or more arrays of sample deposition sites 292to have a regular spacing that is different from one or more otherarrays of sample deposition sites 292. It may also be desirable for oneor more arrays of sample deposition sites 292 to have a regular spacingthat is off pitch or out of phase from the pitch or phase one or moreother arrays of sample deposition sites 292. For some embodiments, theferrous metal disc 286 may be made from steel, stainless steel, nickelas well as other suitable ferrous metals. The disc 286 may have athickness of about 0.01 inches to about 0.1 inches, and a surface areaof about 0.08 square inches to about 0.15 square inches.

For some embodiments of the chips 274, the sample deposition sites 292may include mass spectrometry sample deposition sites, such as MALDIsample deposition sites, which may be arranged in one or more regularlyspaced patterns or arrays. For some embodiments, the chip 274 mayinclude a first array of sample deposition sites 292 for sampleprocessing and a second array of sample deposition sites 292 forcalibration of the processing equipment. For some embodiments, theregular spacing of the second array of calibration sample depositionsites 292 may be off-pitch from the regular spacing of the first array,as will be discussed in more detail below.

For many of the applications of the robotic sample transfer device 10,it is very important to determine the position of the translatablecarriers 56, 58 and 62, and particularly, the three axis translatablecarrier 56 relative to the work surface 22 and functional elements ofthe work surface 22. This is very important so that each pin tool of thepin tool head assembly 64 may be moved to a known position relative tothe functional elements with which it must interact in order to transfersamples from one location to another, as well as be moved to knownpositions of the elements of the cleaning block 164 for proper cleaningof the pin tools 68. For example, it may be important for some sampletransfer methods to dip a particular pin tool 68 or set of pin tools 68into sample wells 270 of a microtiter plate 268 to a pre-determineddepth below the upper nominal surface of the microtiter plate 268 andtake up a known amount of sample material. The pin tool 68 must then beaccurately moved to a sample deposition site 292, such as a spectrometrysample deposition site on a chip 274, without hitting or otherwiseinterfering with any other elements or components on the work surface22. The pin tool 68 be brought into precise contact with apre-determined sample deposition site 292 of the chip 274 with apre-determined amount of force to deposit a known amount of sample ontothe sample deposition site 292. The pin tool 68 may then be preciselymoved to the functional elements of the cleaning block 164 and be movedthrough the progression of cleaning functional elements including theultrasonic bath 182, rinse station 172 and vacuum drying station 176.Each of these steps requires that the pin tool 68 be moved over the bath182, respective rinse tube 174 and respective vertical hole or channel244 of the vacuum drying station 176 and moved vertically downward intofunctional coupling with these elements without making contact withadjacent structures.

For some embodiments of chips 274, such as some of the spectrometry chipembodiments discussed above, it may be desirable to use features of thechip 274 to facilitate the process of locating or positioning the threeaxis translatable carrier with respect to the work surface 22 andfunctional elements of the work surface 22. Some methods of registeringthe position of a pin tool head assembly 64, and pin tools 68 thereof,of a robotic sample transfer device 10 relative to sample depositionsites 292 on a chip 274 include making use of functional elements havingan upper nominal surface at the same z-axis level, for sample transferdevice embodiments that have this feature. That is, some embodiments ofrobotic sample transfer devices 10 have a work surface 22 with aplurality of functional elements, at least two, three, four or more ofwhich have nominal upper surfaces at substantially the same z-axislevel. Such robotic sample transfer devices 10 may also have a threeaxis robotic positioning system 18 with an imaging camera 132 and pintool head assembly 64 secured to a translatable carrier thereof. Forsuch embodiments, the nominal upper surfaces of functional elementsdisposed on work surface 22 may be imaged with the camera 132 and theimage data of the nominal upper surfaces of the functional elements fromthe camera processed by an image processor or the like to determine theapproximate position of the pin tool head assembly 64 relative to thefunctional elements.

For some embodiments of the robotic sample transfer device 10, thecontroller 28 may include an image processor either as a separatecomponent or built into the processor thereof which may be coupled tothe imaging camera 132. The approximate position data obtained by theimaging camera 132 may be used to move the camera 132 to a first chip274 having an array of regularly spaced sample deposition sites 292 andan array of regularly spaced fiducial marks 294 disposed between thesample deposition sites 292. Thereafter, the fiducial marks 294 on thefirst chip may be imaged with the imaging camera 132 and the image dataof fiducial marks 294 on the first chip 274 processed by the imageprocessor. As the fiducial marks 294 on the chip 274 are at knownpositions relative to the sample deposition sites 292 on the chip 274,the positions of the sample deposition sites 292 may then be determinedto a high degree of accuracy. After the fiducial marks have been imaged,feedback regarding a position of the pin tool head assembly 64 may beobtained from one or more linear encoders of three axes of a three axisrobotic positioning system. Position may also be obtained from thecontroller 28 which has tracked the movement of a translatable carrier,such as translatable carrier 56 after carrying out the homing procedurediscussed above.

The position data feedback may then be compared with image processingfeedback and look up table data to determine the precise position of thepin tools 68 of the pin tool head assembly 64 relative to the sampledeposition sites 292 on the first chip 274. This process may then berepeated for one or more other chips 274. Such methods may be used todetermine the precise position of the pin tools 68 of the pin tool headassembly 64 with respect to the sample deposition sites 292 on the firstchip 274 is determined to within about 1 micron to about 10 microns forsome embodiments.

For some embodiments, the location of one or more of the pin tools 68 ofthe pin tool head assembly 64 is known with respect to the position ofthe center of field of view or other reference point in the field ofview of the imaging camera 132. This position information may be storedin a look up table or the like of the processor. For these embodiments,once the imaging camera 132 images a known feature of a functionalelement, for example a sample well in the “A-1” position of a microtiterplate, in the center of field of view of the camera the positioninformation may then be used to calculate the position the one or morepin tools 68 in the center of the A-1 well for future processingmethods. If the relative position or positions of other features on thework surface 22 are known relative to the imaged feature, then theposition of these features may also be calculated. For example, once theposition of the “A-1” sample well of a selected microtiter plate isknown, then the relative positions of the remaining wells of themicrotiter plate may also be calculated.

If the position of the other functional elements of the work surface 22,such as the ultrasonic bath 182, rinse tubes 174, vertical holes 244 ofthe vacuum drying station 176, microtiter places 268 mounted tomicrotiter plate mount blocks 264 in addition to the wells 270 of theplates 268 are known with respect to the position of the imaging cameracenter of field of view or some other reference position in the imagingcamera field of view and this position data is stored in a look upchart, then the position of any of the functional elements relative toone or more of the pin tools 68 of the pin tool head assembly 64 can bedetermined by the controller 28. Thus, the controller may then use theposition information to move one or more of the pin tools 68 or otherdevices secured to the z-axis translatable carrier to the functionalelements for various processing methods. The initial positioning of thecenter of field of view or other reference point of the imaging camera132 may be carried out manually in order to teach the controller withregard to the position of each of the functional elements. For somefunctional element embodiments, such as embodiments of the ultrasonicbath 182 of the ultrasonic wash station, precise position data may notneed to be generated as the bath is sufficiently large to accommodatethe pin tools 68 of the pin tool head assembly 64 with a relativelylarge amount of space around the pin tools 68

The wash fluid supply tank 242 may be disposed in the lower storage tankchamber 44 below the work surface 22 and processing chamber 14 as shownin FIG. 3. An external wash fluid supply tank coupling may be disposedon or in fluid communication with the wash fluid supply tank 242 foroptionally coupling additional capacity to the internal wash fluid tank242. As discussed above, the wash fluid tank 242 is coupled to the rinsetubes 174 of the rinse station 172 by flexible tubing through a fluidpump 238 shown in FIG. 12. The wash fluid supply tank 242, as shown inmore detail in FIG. 14 may have a substantially rectangular shape havinga length of about 10 inches to about 25 inches, a width of about 5inches to about 10 inches, and a height of about 4 inches to about 8inches. The wash fluid tank 242 may be made from lightweight durablepolymer materials such as polyethylene, polypropylene and the like andmay have a capacity of about 1 liter to about 10 liters, morespecifically, about 2 liters to about 4 liters. The wash fluid tank 242may include a liquid level sensor disposed in a wall of the tank 242that is configured to measure the level of fluid disposed within thetank. The tank may also include a removable access cover or plate thatis generally disposed on a top surface of the tank and configured toallow access by an operator to the interior volume of the tank forcleaning, maintenance etc. The tank may also include two or moreorifices for fluid communication with fill tubes, drain tubes and thelike.

The waste fluid storage tank 224 may also be disposed in the lowerstorage tank chamber 44 below the work surface 22 and processing chamber14 adjacent the rinse fluid supply tank 242, as shown in FIG. 3. Anexternal waste fluid storage tank coupling may be disposed on orotherwise in fluid communication with the waste fluid storage tank 224for optionally coupling additional capacity to the internal waste fluidstorage tank 224. As discussed above, the waste fluid tank 224 is influid communication with the gravity drain 228 of the rinse station 172by flexible tubing. The waste fluid tank 224 is also in fluidcommunication with the ultrasonic wash bath 182 of the ultrasoniccleaning station 166 through a flexible tubing and fluid pump 222 thatmay be used to drain the ultrasonic bath 182. The waste fluid storagetank 224, as shown in more detail in FIG. 13 may have a substantiallyrectangular shape having a length of about 10 inches to about 25 inches,a width of about 5 inches to about 10 inches, and a height of about 4inches to about 8 inches. The wash fluid tank 224 may be made fromlightweight durable polymer materials such as polyethylene,polypropylene and the like and may have a capacity of about 1 liters toabout 100 liters, more specifically, about 2 liters to about 4 liters.The waste fluid tank 224 may include a liquid level sensor disposed in awall of the tank 224 that is configured to measure the level of fluiddisposed within the tank. The tank may also include a removable accesscover or plate that is generally disposed on a top surface of the tankand configured to allow access by an operator to the interior volume ofthe tank for cleaning, maintenance etc. The tank 224 may also includetwo or more orifices for fluid communication with fill tubes, draintubes and the like. Either or both of the wash fluid supply tank 224 andwaste fluid tank 242 may be coupled to visual tank fluid levelindicators (not shown) on side walls of the housing 12 in order to allowan operator of the system to quickly and intuitively check the fluidlevels of the tanks 224 and 242. For some embodiments, the visualindicators may include lengths of clear tubing coupled to the interiorcavity of the tanks and extending along a vertical slot cut in therespective side wall of the housing with the end of the clear tubingextending to a location above the top of the tank to which it iscoupled. The clear tubing disposed adjacent the vertical slot may alsocontain a floating ball to visually highlight the level of liquid in theclear tubing.

Referring again to FIG. 12, the pump housing assembly 296 is shown thatincludes the fluid pump 238 used for moving rinse fluid from the washfluid supply tank to the rinse tubes 174 of the fluid rinse station 172.A vacuum pump 298 coupled to the vacuum storage tank 248 and configuredto generate a vacuum within an interior volume of the vacuum storagetank 248 is also disposed within the pump housing 296. The fluid pump222 coupled between the ultrasonic wash bath 182 and waste fluid storagetank 224 is also disposed within the housing 296. A solenoid valve 299for coupling the vacuum within the interior volume of the vacuum storagetank 248 to the vacuum drying orifices 178 of the vacuum drying station176 is also disposed in the pump housing assembly 296. The rinse fluidpump 238, vacuum pump 298, solenoid valve 299 and ultrasonic bathemptying pump 222 may all be coupled to and controlled by the controller28 so as to be activated and stopped at appropriate times or intervalsfor proper cleaning of pin tools 68 or other end results.

For some applications of system calibration as well as other methods ofuse of the robotic sample transfer device embodiments 10, it may bedesirable to have a single pin tool 68 of a pin tool array of a pin toolhead assembly 64 deployed or otherwise configured for use. It may alsobe desirable to have a reduced number of pin tools 68 of a pin toolarray configured for use, while the remaining pin tools of the pin toolarray are disposed in a retracted state in an upward direction orotherwise deactivated from use. For some embodiments of pin tool headassemblies 64, a pin tool displacement block may be used to selectivelyretract one or more pin tools 68 of a pin tool array in a proximal orupward direction so as to leave only the desired active pin tools 68extending downward and configured for use.

Some embodiments of a pin tool displacement block for selectivelydisplacing at least one pin tool 68 of a pin tool head assembly 64 of arobotic sample transfer device 10 in an axial direction include a blockbody having a bottom surface and a plurality of parallel slots formedinto the block body portion. The parallel slots may be substantiallyperpendicular to the bottom surface with a predetermined regular spacingconfigured to correspond to regular spacing of pin tools 68 of a pintool head assembly 64. The parallel slots may have a transversedimension which is sized to allow easy movement of a width of a nominalshaft of the pin tools in the slots but restrictive of movement of anenlarged portion of the shaft of the pin tools.

The block body portion may also include at least one relieved portion orchannel that may extend from the top surface of the block body portionin a direction which is substantially perpendicular to the bottomsurface in one or more of the parallel slots. The relieved portion mayhave a transverse dimension sized to allow easy movement in an axialdownward direction of not only the nominal shaft portion of a respectivepin tool 68 but also and enlarged portion of a pin tool shaft and beconfigured to mechanically capture the enlarged portion of a pin tooldisposed therein in a lateral direction. The enlarged portion of the pintool shaft may be greater in transverse dimension than the transversedimension of the slot but less in transverse dimension than a transversedimension or diameter of the relieved portion and which extends from atop surface of the block body towards the bottom surface. For someembodiments, the parallel slots may have a width of about 0.04 inches toabout 0.2 inches, more specifically, about 0.07 inches to about 0.1inches, and a spacing or pitch of about 0.1 inches to about 0.5 inches,more specifically, about 0.15 inches to about 0.2 inches. Someembodiments may have a slot length of about 0.2 inches to about 2inches, more specifically, about 0.5 inches to about 1.2 inches, andeven more specifically, about 0.7 inches to about 1 inch. For someembodiments, the relieved portion or channel may have a diameter ortransverse dimension of about 0.1 inches to about 0.3 inches, morespecifically, about 0.15 inches to about 0.25 inches, and even morespecifically, about 0.18 inches to about 0.22 inches.

For some embodiments, the enlarged portion of a shaft of a pin tool 68may include a collar member and the stop surface of the at least onerelieved portion may be configured to prevent axial movement of thecollar member and mechanically capture a collar disposed therein memberto prevent lateral displacement of the block body when the block isdeployed in a pin tool head assembly 64. If more than one relievedportions or channels are disposed in a single block body portion, it maybe desirable for the relieved portions to have a regular spacing thatcorresponds to a regular spacing of the pin tools 68 of a pin tool headassembly 64 for which the block is to be used.

For some embodiments, the relieved portion or channel may extend eitherpartially or completely from the top surface of the block body portionto the bottom surface of the block body portion. For some embodimentswherein the relieved portion extends only partially from the top surfaceof the block body portion, the relieved portion may terminate at a stopsurface which is spaced from the bottom surface. The top surface andbottom surface of the block body portion may be substantially flat andsubstantially parallel to each other for some embodiments. Someembodiments of pin tool displacement blocks may have a reversibleconfiguration wherein when the block is oriented in a first directionand deployed, a first pin or set of pins is active and when flipped over180 degrees or otherwise oriented a second direction and deployed, asecond pin or set of pins is active which is different from the firstset. For such embodiments, it may be desirable for the relieved portionsto extend only partially from a first surface to a second surface of theblock body portion.

Embodiments of the block body portion may optionally include a handlemember extending from and secured to the body portion for moreconvenient handling by a user of the device. The handle member may be athin but rigid extension of the material of the block body portion thatis easily gripped by a user and extends away from the block body portionwith material relieved from both the top surface and bottom surface toallow easy access and gripping. The block body may be made from an inertmaterial, such as Teflon®, Delrin® or the like and may have a width ofabout 0.4 inches to about 3 inches, more specifically, about 0.8 inchesto about 1.2 inches, a length of about 0.5 inches to about 4 inches,more specifically, about 1.5 inches to about 2.5 inches, and a height orthickness of about 0.2 inches to about 1.5 inches, more specifically,about 0.3 inches to about 0.7 inches.

FIGS. 15 and 16 illustrate a simplified pin tool displacement block 300having a single slot 302 with a single relieved portion or channel 304disposed in the slot 302. The relieved portion 304 extends from a topsurface 306 of the block body 308 portion towards a bottom surface ofthe block body portion and extends through the block body portion 308completely from the top surface 306 to a bottom surface 312, as shown inFIG. 16. The pin tool displacement block 300 may have the same orsimilar features, dimensions or materials as the features, dimensions ormaterials of the pin tool displacement block embodiments discussedabove.

FIG. 17 is an elevation view of a simplified pin tool head assembly 314having a first pin tool 316 and second pin tool 318 mounted in a frame322 of the pin tool head assembly 314. The frame 322 includes a firstside plate 324, a second side plate 326, a bottom plate 328 and a coverplate 330. All four plates are secured to adjacent plates at their endsin a perpendicular orientation. The first and second side plates 324 aresubstantially parallel to each other and the cover plate 328 and bottomplate 330 are substantially parallel to each other. The pin tools 316and 318, which may have the same or similar features, dimensions ormaterials as the features, dimensions or materials of the pin toolembodiments 68 discussed above, have a “D” shaped transverse crosssection in an upper portion that mates with a corresponding “D” shapedhole in the cover plate 330. A resilient member in the form of a helicalspring 152 is disposed over each pin tool 316 and 318 between the coverplate 330 and washer 154 disposed towards the bottom of each pin tool316 and 318. The washers 152 of the pin tools 316 and 318 are heldaxially in place by compression clips or collar members 144 that aresecured to circumferential grooves 148 in an outer surface of each pintool shaft 142. As such, each pin tool 316 and 318 is resiliently biasedin a downward direction both by the weight of the pin tool itself andthe helical spring 152. The helical springs 152 have an axial length ina relaxed uncompressed state that is longer than the distance between aninside surface of the cover plate 330 and inside surface of the bottomplate 328.

FIGS. 18 and 19 illustrate an embodiment of a method of displacing a pintool of the pin tool head assembly 314 of a robotic sample transferdevice with the pin tool displacement block 300 discussed above. Asshown in FIG. 18, the pin tool head assembly 314 is brought downvertically into contact with a flat surface 332 in order to displace thepin tools 316 and 318 axially in an upward direction. In this position,the enlarged portions of the pin tool shafts or collar members aredisplaced axially from the inside surface of the bottom plate 328 asshown. The slot 302 of the pin tool displacement block 300 is thenaligned with the row of pin tools 316 and 318 and advanced into the pintool head assembly 314 as shown by arrow in FIG. 18. Once the relievedportion 304 in the slot 302 of the pin tool displacement block 300 isaligned coaxially in a vertical direction with the first pin too shaft316, the pin tool head assembly 314 may then be raised and retractedfrom the flat surface 332 to allow the pin tools 316 and 318 of the pintool head 314 assembly to resume a relaxed state. As the pin tool shafts316 and 318 return to their nominal relaxed positions, the collar member144 of the first pin tool 316 passes through the relieved portion 304 ofthe pin tool displacement block 144 and comes to rest on the insidesurface of the bottom plate 328. However, the collar member 144 of thesecond pin tool 318 comes to rest on the upper surface of the pin tooldisplacement block 300 in an axially retracted state with the distal tipof the pin tool axially retracted from the plane of the first pin toolby a length, indicated by arrow 334, which is substantially equal to thethickness or height of the pin tool displacement block 300.

FIGS. 20A-20D illustrate an embodiment of a pin tool displacement block336 for use with a 6×4 pin tool array of a pin tool head assembly 64.The pin tool displacement block 336 includes 6 parallel slots 338 thathave a regular spacing that is configured to match that of an array ofpin tools of a pin tool head assembly 64. A single relieved channel 342is disposed in a second parallel slot 338 of the block 336 in order toallow a single pin tool in a 2-2 position of the array to be configuredfor use after deployment of the pin tool displacement block into the pintoo head assembly. The pin tool displacement block 336 may have some orall of the features, dimensions or materials as the features, dimensionsor materials of any of the pin tool displacement blocks discussed above.The pin tool displacement block 336 includes a first parallel slot, asecond parallel slot, a third parallel slot, a fourth parallel slot, afifth parallel slot and a sixth parallel slot. The pin tool displacementblock includes a block body 334 having a bottom surface 346 with the 6parallel slots formed into the block body portion 344 substantiallyperpendicular to the bottom surface 346 with a predetermined regularspacing that may be configured to correspond to regular spacing of pintools 68 of a pin tool head assembly 64. The parallel slots 338 may havea transverse dimension which is sized to allow easy movement of a widthof a nominal shaft of the pin tools 68 in the slots 338 but restrictiveof movement of an enlarged portion 143 of the shaft of the pin tools 68.For some embodiments, the parallel slots 338 may have a width of about0.04 inches to about 0.02 inches, more specifically, about 0.07 inchesto about 0.1 inches, and a spacing or pitch of about 0.1 inches to about0.5 inches, more specifically, about 0.15 inches to about 0.2 inches.Some embodiments may have a slot 338 length of about 0.2 inches to about2 inches, more specifically, about 0.5 inches to about 1.2 inches, andeven more specifically, about 0.7 inches to about 1 inch. For someembodiments, the relieved portion or channel 342 may have a diameter ortransverse dimension of about 0.1 inches to about 0.3 inches, morespecifically, about 0.15 inches to about 0.25 inches, and even morespecifically, about 0.18 inches to about 0.22 inches.

The relieved channel 342 extends from the top surface 348 completelythrough the block body portion 344 in a direction which is substantiallyperpendicular to the bottom surface 346. The relieved channel or portion342 may have a transverse dimension sized to allow easy movement in anaxial downward direction of not only the nominal shaft portion of arespective pin tool 68 but also and enlarged portion 143 of a pin toolshaft and be configured to mechanically capture the enlarged portion 143of a pin tool 68 disposed therein in a lateral direction. Embodiments ofthe block body portion 344 may optionally include a handle member 352extending from and secured to the body portion for more convenienthandling by a user of the device. The handle member 352 may be a thinbut rigid extension of the material of the block body portion 344 thatis easily gripped by a user and extends away from the block body portionwith material relieved from both the top surface 348 and bottom surface346 to allow easy access and gripping. The block body 344 may be madefrom an inert material, such as Teflon®, Delrin® or the like and mayhave a width of about 0.4 inches to about 3 inches, more specifically,about 0.8 inches to about 1.2 inches, a length of about 0.5 inches toabout 4 inches, more specifically, about 1.5 inches to about 2.5 inches,and a height or thickness of about 0.2 inches to about 1.5 inches, morespecifically, about 0.3 inches to about 0.7 inches.

FIGS. 21A-21D illustrate an embodiment of a pin tool displacement block360 for use with a 6×4 pin tool array. The pin tool displacement block360 includes 6 parallel slots 362 that may have a regular spacing thatis configured to match that of an array of pin tools of a pin tool headassembly 64. Two relieved channels 364 are disposed in each of a secondparallel slot, a fourth parallel slot, and a sixth parallel slot inorder to allow six pin tools to be configured for use after deploymentof the pin tool displacement block into the pin too head assembly. Otherthan the 6 relieved channels 364, the pin tool displacement block ofFIGS. 21A-21D may have the same features, dimensions or materials asthose of the pin tool displacement block of FIGS. 20A-20D discussedabove. The relieved channels of the pin tool displacement block aredisposed at the 2-2, 2-4, 4-2, 4-4, 6-2 and 6-4 positions of the arrayand extend completely through the block body portion of the pin tooldisplacement block 360.

For some embodiments, a method for selectively displacing at least onepin tool 68 of a pin tool head assembly 64 of a robotic sample transferdevice 10 may include the use of a pin tool displacement block 370having a block body with a bottom surface and a plurality of parallelslots formed into the block body portion. The parallel slots may besubstantially perpendicular to the bottom surface with a predeterminedregular spacing configured to correspond to regular spacing of pin tools68 of a pin tool head assembly 64. The parallel slots may have atransverse dimension sized to allow easy movement of a width of anominal shaft of the pin tools 68 in the slots but restrictive ofmovement of an enlarged portion of the shaft of the pin tools. The pintool displacement block may also include at least one relieved portionor channel in a slot which has a transverse dimension sized to alloweasy downward movement of the enlarged portion of a pin tool shaft whichis greater than the transverse dimension of the slot and which extendsfrom a top surface of the block body towards the bottom surface. Anarray of pin tools of a pin tool head assembly 64 are axially displacedby depressing the distal ends of the pin tools 68 against a flatsurface. The pin tool displacement block may then be deployed into thepin tool head assembly such that the parallel slots of the pin tooldisplacement block slide over rows of the array of pin tools of the pintool head assembly. The pin tools 68 are then allowed to return to arelaxed state by retracting the pin tool head assembly from the flatsurface with at least one of the pin tools remaining displaced in anaxially retracted and relaxed state.

FIGS. 22-24 illustrate an embodiment of a reversible pin tooldisplacement block 370. The reversible pin tool displacement block 370may have some or all of the features, dimensions or materials as thoseof the pin tool displacement block embodiments 300, 336 and 360,discussed above. The reversible pin tool displacement block 370essentially combines the functions of the pin tool displacement blocks336 and 360 of FIGS. 20A-20D and FIGS. 21A-21D discussed above. When theblock 370 is oriented in a first direction and deployed, a first pintool or set of pin tools is active and when the block is flipped over180 degrees or otherwise oriented a second direction and deployed, asecond pin tool or set of pin tools is active which is different fromthe first set. The reversible pin tool displacement block embodiment 370shown allows a single pin tool to be configured for used while deployedon a first side 372 while maintaining all remaining pin tools of a 6×4pin tool array in a retracted state. The reversible pin tooldisplacement block 370 allows 6 pin tools to be configured for usedwhile deployed on a second side 374 while maintaining all remaining pintools of a 6×4 pin tool array in a retracted state.

For the reversible pin tool displacement block embodiment 370, it may bedesirable for relieved portion or portions 376 to extend only partiallythrough the block body portion 370 and terminate at a stop surface 378which is spaced from a surface of the block opposite the opening of therelieved channel 376. The first surface 372 and second surface 374 ofthe block body 370 portion may be substantially flat and substantiallyparallel to each other for some embodiments. FIG. 22 illustrates the pintool displacement block 370 with the first side 372 up showing 6relieved channels 380 that allow six pin tools 68 to be active or usablewhen the pin tool block 370 is deployed on the second side 374 with thesecond side down. FIG. 24 illustrates the pin tool displacement block370 with second side 374 up showing a single relieved channel 382 thatallow a single pin tool to be active or usable on the first side whenthe first side is down.

Some method embodiments of dispensing calibration material onto a chip274, such as a spectrometry chip, may include the use of a chip 274having an array of regularly spaced sample deposition sites 292 disposedon a substantially flat working surface 293 of the chip 274. The chip274 may also include at least one sample deposition site 292 forreceiving calibration material which is also disposed on the flatworking surface 293 of the chip 274. The method embodiments may includethe use of a robotic sample transfer device 10 having a pin tool headassembly 64 with an array of regularly spaced pin tools 68. Distal ends158 of the pin tools 68 of the pin tool head assembly 64 are disposedsubstantially coplanar in a relaxed state and have a regular spacingwhich is the same as or otherwise matched to the regular spacing of thefirst array of sample deposition sites 292 of the chip. The spacing ofthe pin tools 68 may also be an integer multiple of the spacing of thesample deposition sites of the chip 274 and configured to align with thearray of regularly spaced sample deposition sites 292 of the chip 274 ora subset thereof.

Generally, it is desirable to dispense calibration material veryselectively to only those sample deposition sites 292 that are intendedfor use with calibration materials. As such, it is desirable to avoiddispensing calibration material or otherwise contaminating sampledeposition sites 292 which are not intended for use in calibration withcalibration material. For some method embodiments, it may be useful touse a reduced number of pin tools 68 of a pin tool head assembly 64 inorder to avoid such contamination or inadvertent material transfer. Forsome such method embodiments, all but one of the pin tools 68 of the pintool head assembly 64 is displaced to a retracted non-usable state bydeploying a pin tool displacement block 336, such as pin tooldisplacement block shown in FIGS. 20A-20D, into the pin tool headassembly 64. The pin tool block 336 may be deployed in the pin tool headassembly 64 as shown in FIGS. 18 and 19 and discussed in theaccompanying text above. A sample reservoir 156 of the usable pin tool68 of the robotic sample transfer device 10 may then be loaded withcalibration material by dipping the pin tool 68 into a well containingcalibration material. The calibration material may then be dispensedfrom the usable pin tool 68 of the robotic sample transfer device 10 toa sample deposition site 292 for receiving calibration material. Duringthe deposition of the calibration material to the sample deposition site292, the functioning pin tool 68 containing the calibration materialextends distally below the pin tools 68 that are held in a retractedstate by the pin tool displacement block 336. As such, while thefunctioning pin tool tip 156 is moved distally into contact with thesample deposition site 292 for deposition of the calibration material,the pin tools 68 which are displaced by the pin tool displacement block336 do not contact the chip.

In addition to dispensing calibration materials by methods that includecontrolling the number of active pin tools 68 of a pin tool array 64,calibration material may also be deposited on selected sample depositionsites 292 of a chip 274 or the like by using a full array of pin tools68. The full array of pin tools 68 may be used with a chip 274 having afirst array of regularly spaced sample deposition sites 292 disposed ona substantially flat working surface 293 of the chip 274. The chip 274may also have at least one sample deposition site 292 for receivingcalibration material which is also disposed on the flat working surface293 of the chip 274 and which is off pitch with respect to the regularspacing of the first array of regularly spaced sample deposition sites292 of the chip 274, as shown in FIGS. 11A and 11B.

A robotic sample transfer device 10 having a pin tool head assembly 64may also be used for the calibration method. The pin tool head assembly64 may have an array of regularly spaced pin tools 68 with distal ends158 which are substantially coplanar with each other in a relaxed state.The pin tools 68 of the pin tool array also have a regular spacing whichis the same as or otherwise corresponds to the regular spacing of thefirst array of sample deposition sites 292 or an integer multiplethereof. The regular spacing of the pin tools 68 is also configured toalign with the array of regularly spaced sample deposition sites 292 ofthe chip 274 or a subset thereof.

During a calibration process embodiment, sample reservoirs 156 of thearray of regularly spaced pin tools 68 of the robotic sample transferdevice 10 may be loaded with calibration material. Only the pin toolreservoir or reservoirs 156 that will be depositing the calibrationmaterial onto the desired calibration material sample deposition sitewill be loaded with calibration material for some embodiments. Thecalibration material may then be dispensed from the pin tools 68 of therobotic sample transfer device 10 to the at least one sample depositionsite 292 for receiving calibration material. During deposition of thecalibration material, the pin tools 68 which are not aligned with sampledeposition sites 292 for receiving calibration material are off pitchwith respect to the first array of regularly spaced sample depositionsites 292 of the chip. As such, the pin tools 68 do not contact any ofthe regularly spaced sample deposition sites 292 of the first array.FIG. 25 illustrates two pin tool distal ends 158 disposed over sampledeposition sites 292 of a second array of sample deposition sites whichare regularly spaced and off pitch from the first array. The sampledeposition sites 292 of the second array are configured to receivecalibration material which is being dispensed from the sample reservoirs156 of the distal tips 158 of the pin tools 68 to the calibration sampledeposition sites 292 of the chip 274 as shown. Also shown are two pintool distal ends 158 disposed between and not aligned with the sampledeposition sites of the first array of sample deposition sites 292 forreceiving normal sample deposition. For some embodiments, the firstarray of regularly spaced sample deposition sites includes an array ofregularly spaced mass spectrometry sample deposition sites.

FIG. 26 illustrates a main screen of an embodiment of the user interface26 discussed above. The main screen or main menu is arrived at after auser logs onto the device 10 by entering a user name and password intothe system through the user interface 26. From the main screen of theuser interface 26, a user may navigate the various programming controlsof the device 10 in a convenient and user friendly manner. For theembodiment shown, along the top row of the screen, a “home” button 400may be touched by the user to manually send the pin tool head assembly64 of the device 10 to a home position located generally towards thefront and left side of the processing chamber 14. A “system status”button 402 takes the user to a screen that provides detailed informationregarding the current status of the integrated robotic positioningdevice 10. Status data such as the identification of the current user,computer identification, hard drive capacity, volatile memory capacity,software version, x, y, and z positions of the pin tool head assembly64, safety interlock status, temperature and humidity within theprocessing chamber 14, wash fluid tank 242 and waste fluid tank 224fluid levels as well as other information may be displayed on the statusscreen or screens. The “exit” button 404 takes the user back to thefundamental operating system interface of the processor 32. For example,for processor embodiments 32 using a Windows® type operating system, theexit button 404 will return the user back to a Windows® desktop. A“help” button 406 allows the user to access a help database withinformation regarding the programming, use and operation of the device10 with regard to the type of options available on the screen displayingthe help button 406. Generally, for some embodiments, each screen of theuser interface 26 may have a help button 406. At the bottom row of themain screen, a “log off” button 408 is used to log off the currentlogged on user of the system 10. A “shut down” button 410 shuts down thesystem 10.

A “maintenance” button 412 on the main screen takes a logged on user toa maintenance screen illustrated in FIG. 27. The maintenance screenincludes the status button 402, exit button 404 and help button 406discussed above. The maintenance screen also includes a “load chips andMTPs” button 414, a “load solution” button 416, a “fill supply tank”button 418, a “clean pins” button 420, a “complete cycle” button 422, a“drain solution” button 424, an “drain supply tank” button, 426 and a“condition pins” button 428. The load chips and MTPs button 414 movesthe pin tool head assembly 64 of the system 10 to a far left and rearposition in order to make room for the user to load sample chips 274 ora chip block 266 onto the work surface 22 of the device 10. The loadsolution button 416 moves the pin tool head assembly 64 to the far rightand rear position of the processing chamber 14 in order to make room fora user to load or unload the supply reservoir 168. The fill supply tankbutton 418 prompts the user to position the fluid valves in the lowerstorage tank chamber 44 in communication with the supply tank such thatthe supply tank 242 may be filled from an external tank. After the useris prompted to manually configure the valves, de-ionized water may bepumped into the supply tank with a self priming pump disposed within thehousing 12. The pump may be configured to automatically turn off oncethe tank 242 is filled. The user may then be prompted to switch thevalves manually back normal operating mode. The controller may thenexecute a priming routine to clean out air from the tubing or linesbetween the tank 242 and the rinse station. To accomplish this, thewater may be pumped to the rinse station at about 5 percent to about 10percent normal flow using a pulsed modulation technique. For this pulsedtechnique, the pump may be run at full speed for a short period of timeand then stopped for an interval before restarting again. For someembodiments, the pump may be run for about 5 msec to about 15 msec andstopped for about 85 msec to about 95 msec. The pulse intervals areshort enough that the pump appears to run continuously to the user, butis only achieving a 5 percent to 10 percent duty cycle.

The clean pins button 420 runs a protocol for cleaning the pins 68 ofthe pin tool head assembly 64 by immersing the pins in the ultrasonicbath for an extended period of time. For some embodiments, the pin tools64 may be soaked for about 15 minutes to about 45 minutes, morespecifically, for about 25 minutes to about 35 minutes. During thesoaking process, the ultrasonic bath may contain a cleaning solutionsuch as pure ethanol. The pin tools may be treated with a subsequentstandard cleaning cycle after the soak that may include a water rinse inthe rinse station, drying in the vacuum drying station, ultrasoniccleaning with water in the ultrasonic bath and a final drying in thevacuum drying station.

A complete cycle button 422 initiates a standard cleaning cycle, asdiscussed above, including a water rinse in the rinse station, drying inthe vacuum drying station, ultrasonic cleaning with water and alcohol inthe ultrasonic bath and a final drying in the vacuum drying station. Forsome embodiments, an equal mix of de-ionized water and ethanol alcoholmay be used for the ultrasonic cleaning bath. The drain solution button424 turns on the pump 222 and drains the ultrasonic bath of theultrasonic wash station. As the ultrasonic bath is drained, it may berefilled by the reservoir 168 until the reservoir is emptied.

The drain supply tank button 426 turns on the rinse fluid pumpcontinuously until the rinse fluid supply tank 242 is emptied. This maybe used to lighten the device 10 in anticipation of transporting thedevice 10, performing maintenance in the lower chamber or the like. Thecondition pins button 428 initiates a protocol whereby the pins 68 ofthe pin tool head assembly 64 are soaked in a cleaning solution, such asa 1 molar solution of NaOH which may be disposed within selected wellsof a microtiter plate. The pins 68 may be soaked for about 5 minutes toabout 15 minutes and then treated with a standard clean cycle asdiscussed above. This process may be carried out every week or so inorder to condition the pins 68.

Referring back to FIG. 26, a “mapping” button 430 takes the user to amapping screen shown in FIG. 28. The mapping screen allows the user toinput some preliminary information about the sample transfer processdesired. For example, for some embodiments, the user may be promptedwith a request to select a microtiter plate format, such as a 96 or 384well plate. Next, the user may be prompted to select a chip format andthereafter the number of the chips to be used. Once this information hasbeen entered, mapping information presented visually by a grid 432representing the microtiter plate wells and grid 434, representing thechip sample deposition sites, may be selected and stored by a “save”button 436 to track the mapping to be used. Chip buttons 438 may be usedto select the chip number to be loaded with samples taken and the “MTP”arrow buttons 439 may be used to select the microtiter plate from whichto load samples. The “exit” button 440 may be used to exit the mappingscreen. In addition, a two dimensional bar code of a selected chip 274may be tied to a bar code of a specific microtiter plate by thecontroller. The controller may also store the mapping configurationselected between the chip and microtiter plate along with someadditional data including time stamp data, microtiter plate and chipconfiguration data and the like. All of this data may be transferred toa sample tracking database server or other data storage device.

Referring again to FIG. 26, a “methods” button 442 takes the user to amethods screen shown in FIG. 29. The methods screen includes the exitbutton 404, status button 402 and help button 406 on the top row whichmay have the same functions as discussed above. Also on the top row ofthe methods screen are an “open” button 442 and a “save” button 444. Theopen button 442 allows a user to open a predetermined set of methodtransfer parameters and the save button 444 allows a user to save apredetermined set of method transfer parameters. A “run transfer” button443 takes the user to the “run transfer” screen shown in FIG. 30 anddiscussed below. At the bottom of the methods screen are three tabs,with the “setup” tab 445 being selected for the methods screenembodiment shown. Within a “mapping file” section 446 of the methodsscreen for setup, a user may select a predetermined mapping file asgenerated from the mapping screen of FIG. 28 for use in a transfermethod. A “browse” button 448 may be used to browse a plurality ofpredetermined mapping files created by a user. An “analysis” section 450of the methods screen includes a “volume check” check box 452 and a“sample tracking” check box 454. If the user selects the volume checkbox 452, each sample deposited onto a sample deposition site of a chip274 may be imaged by the imaging camera and the image taken processed inorder to estimate the volume of each sample deposited onto a sampledeposition site. The volume check parameters of a deposited sample maybe determined by the volume, average diameter, y-axis directiondiameter, x-axis direction diameter, circumference and area of one ormore deposited samples. The average volume for samples deposited andstandard deviation of volume of samples deposited may also bedetermined. If the sample tracking box is checked by a user, bar codedata associated with microtiter plates 268 and corresponding chips 274will be saved to a file that may be later accessed by a user in order toconfirm a transfer method.

A “scout plate” section 456 allows a user to select a particular chiptype from the number of chips such as a 4 chip scout plate or a 10 chipscout plate. A “spectrochips” section 458 includes “chip selection”buttons 460 numbered 1-10 for a 10 chip mount block (or 1-4 if a 4 chipmount block was selected in section 456) which allows a user to select aparticular chip from the number of chips of the chip mount block typepreviously selected to receive transferred samples for a particularmethod.

Referring again to the bottom of the methods screen, if the “cleaning”tab 462 is selected for the screen, additional sections (not shown) areavailable to the user which allow a user to set cleaning cycleparameters such as dwell time in a particular cleaning stationfunctional element and the like. The “aspirate/dispense” tab 464provides options on a screen (not shown) for the amount of time that thesample reservoir of the pin tools 68 dwell in a sample reservoir whileaspirating a sample, the depth to which a pin tool 68 is moved into asample well of a microtiter plate and the speed of the pin tool 68 as itenters and leaves a sample well of a microtiter plate. The user may alsoset the dwell time of a pin tool 68 as it contacts a sample depositionsite of a chip, the speed of the pin tool as it approaches a surface ofthe chip and the length of compression of the resilient member whichbiases the pin tool 68 against the upper surface of the chip once thetip of the pin tool 68 makes contact. These parameters may affect theamount of sample aspirated or taken up by a pin tool 68 and the amountof sample deposited to a sample deposition site. These parameters mayalso affect the speed and efficiency of the transfer method and preventdamage to the chips 274 or microtiter plates as well as prevent loss ofsamples or contamination due to splashing as a result of excessive speedof the pin tool 68 during a transfer.

Referring again to FIG. 26, a “transfer” button 466 takes the user to arun transfer screen shown in FIG. 30. A top row on the run transferscreen again includes the exit button 404, status button 402, and helpbutton 406 that may have he same functions as discussed above. An “openmethod” button 470 at the top of the screen allows a user to open apreviously determined set of method parameters. A “flow” button 472allows a user to access the method screen while running a transfer andchange method parameters during the transfer process. A “volume check”button 474 allows a user to access and review volume check data for datacollected when the volume check box 452 on the method screen isselected.

A live video image of the transfer process may be displayed in videoblock 476 as well as a graphic of the transfer status of sampledeposition on chips 274 of a selected chip mount block shown on a chipstatus block 478. Microtiter plate status blocks 480 and 482 show thetransfer status of two selected microtiter plates 268 in current useincluding a graphic display of sample wells that have already beentransferred and which wells are full and have not yet been transferredto a sample deposition site of a chip 274. “Stop”, “pause”, “step” and“run” buttons are disposed at the bottom of the run transfer screenwhich allow a user to stop, pause or run a selected transfer process.The step button may pause after every dispense cycle to allow the userto update method parameters or view volume check data. The use may thenpress the step button again to continue the cycle in the transfer orpress the run button to finish the transfer process withoutautomatically pausing after each dispense cycle.

Referring back to FIG. 26, a “configure” button 486 takes the user to aconfigure screen shown in FIG. 31. A top row on the configure screenagain includes the exit button 404, status button 402, and help button406 that may have he same functions as discussed above. Also on the toprow of the configure screen are an “open” button 442 and a “save” button444. The open button 442 allows a user to open a predetermined set ofmethod transfer parameters and the save button 444 allows a user to savea predetermined set of method transfer parameters.

At the bottom of the configure screen, a row of tabs allows the user toselect sub-screens that provide options for selecting movementparameters for various predetermined process steps that the device 10may carry out. The tabs at the bottom of the configure screen include a“calibrant” tab 490, a “dry rinse” tab 492, a “dry wash” tab 494, a“MTP” or microtiter plate tab 496, a “rinse” tab 498, a “spectochip” tab500 and a “wash” tab 502. A tab with a set of laterally oriented arrowsmay be selected to show additional tabs (not shown) including a“general” tab, a “bar code” tab and a “calibration” tab. For each ofthese tabs, generally, motion parameters for the pin tool head assemblyfor the process corresponding to each tab may be selected or preset. forexample, for the configure screen show in which the calibrant tab 490 isselected, the z axis motion acceleration, z axis motion velocity, z downposition and calibrant dip time may be preset and saved. These settingsmay be determined by moving a sliding setting bar 503A disposed in asetting box or by directly entering numerical data in a data box 503Bdisposed below the sliding setting bar. Once these settings are selectedand saved, they may be tested for each process indicated by the tabs byactuating the “test” button 504. Some additional features includefunctions of the barcode tab which allow a user to turn the bar codereader function on and off. The bar code reader function may be carriedout by the bar code reader head for scanning linear bar codes onmicrotiter plates 268 as well as the imaging camera which may be used toscan two dimensional bar codes disposed on the chips 274.

The general tab screen has a variety of settings and also includes abutton which allows a user to reset all of the settings of the configurescreens to the factory default settings. The calibration tab screenprovides the user with predetermined settings that may not be changedoften. For example, the calibration tab screen may provide a data box toenter the position offset of a pre-selected pin tool 68 of the pin toolhead assembly 64, such as pin tool “A-1”, with respect to the positionof the center of the field of view of the imaging camera. Once this isproperly set, any feature, functional element or the like which isimaged by the imaging camera in the center of the field of view may thenbe accessed by a pin tool by instructing the processor to move the pintool 68 in the distance and direction of the known offset, which mayserve as a single entry look up table for such motion.

Referring to FIG. 26, a “motion” button 510 takes the user to a motionscreen shown in FIG. 32. A top row on the motion screen again includesthe exit button 404, status button 402, and help button 406 that mayhave he same functions as discussed above. Also on the top row of theconfigure screen is a “save” button 444 that may be used to storesettings. A home button 400 is also disposed on the motion screen tohave the pin tool head assembly moved to the home position.

The motion screen of FIG. 32 allows a user to select general motionparameters for motion acceleration, velocity and large move distance fortranslation of the pin tool head assembly in the x, y and z axes, withthe buttons for selecting the axis of interest indicated by buttons 512,514 and 516 respectively. Data selections for these parameters may beentered by clicking and moving a sliding bar 518 or by direct data entryinto a data box 520 disposed below the sliding bar 518. Arrows 522disposed on either side of the data boxes allow a user to click thearrows and adjust the parameters in the data boxes by fixed increments.A set of arrows 524 are disposed on the right hand side of the screenand allow a user to manually move or jog the pin tool head assembly bypredetermined increments. A toggle button 526 allows users to selectbetween large movement increments and small movement increments, each ofthe increments being selected or set by the sliding bar 528 or by directdata entry into data box 530. One of the uses of the functions on themotion screen is to teach the processor of the device 10 where thelocations of the various components or functional elements reside on thework surface. For example, a user may wish to teach the processor thelocation of a first microtiter plate disposed on the microtiter platemount block of the work surface. The user may use the jog buttons 524 ineither large movement or small movement mode to position the pin toolhead array 64 above the predetermined corner of the first microtiterplate. Fine adjustments may be made with visual feedback by the user toalign the pin tools 68 with the predetermined wells of the microtiterplate.

Once this positioning has been achieved, the user may select a “check”button 532 disposed at the top of the motion screen which then takes theuser to the “deck plate” screen shown in FIG. 33. A top row on the deckplate screen includes the exit button 404, status button 402, and helpbutton 406 that may have he same functions as discussed above. Also onthe top row of the deck plate screen are an “open” button 442 and a“save” button 444. The open button 442 allows a user to open apredetermined set of method transfer parameters and the save button 444allows a user to save a predetermined set of method transfer parameters.

The deck plate screen also includes a variety of buttons that may beused to allow a user to store position data generated from the positionsensors such as the encoder strip assemblies and store that knownposition data so as to associate the position data to a known componentof functional element of the work surface. There are two basicapproaches to use of the deck plate screen. The first is a manual teachmode which may be entered from the check save button 532 of the motionscreen wherein know position data is stored so as to correspond to knowfunctional elements or components of the device 10. A manual mode in thedeck plate screen allows a user to direct the pin tool head to a known,pre-programmed position and also allows the used to carry out basicsingle event procedures, such as washing, drying, rinsing etc.

If the position information for each of the functional elements of thework surface 22 is taught to the processor, a database or lookup typetable may be generated for use as to absolute and relative positions ofthe functional elements as well as other components. For example, fromthe motion screen of FIG. 32, the pin tool head array may be moved by auser using the jog buttons 524 to the A-1 position of the firstmicrotiter plate disposed on the work surface of the device. Once thepin tools are properly positioned, a “microtiter plate type” button 536may be touched and toggled so as to select a microtiter plate type thatmatches the type mounted to the work surface. For some embodiments, thetoggle choices may include a 96 well or 384 well microtiter plate. A“first microtiter plate” button 538 may then be touched to indicate thatthe pin tools 68 are disposed in the first microtiter plate and not thesecond microtiter plate which may be selected by “second microtiterplate” button 540. A graphic image of the first microtiter plate isdisplayed on block 542 and the second microtiter plate on block 544. Ifthe position data and component selection has been properly made, theuser may then select the “check save” button 546 at the top of thescreen which saves the data to the memory storage unit of the controller28 or other suitable device. This same procedure may be applied to theteaching of position data of the pin tool head assembly and pin tools 68thereof by using the “pin tool” button 548, the bar code reader headassembly by using the “bar code reader” button 550, and the camera byusing the “camera” button 552. These position data teaching proceduresgenerally apply to the pin tool head assembly 64 and microtiter plates,however, the same or similar procedures for teaching position data tothe controller 28 may also be used for the pin tool head assembly 64with respect to the chips 274.

For such a procedure, the pin tool head may be manually moved to apredetermined location with respect to a chip 274 mounted in a chipmount block on the work surface. Such positioning may be carried out byusing manual jogging movement from the position screen discussed above.Once the pin tools 68 are properly positioned with respect to acomponent for functional element, the component or functional elementmay be identified by touching the corresponding button, such as the “pintool” button 553. Thereafter, the type of chip 274 being used may beselected by the “chip type” button 554 to select between a 384 sitechip, a 96 site chip or any other suitable configuration. The specificchip 274 over which the pin tools 68 are located may then be selected bytouching one of the “chip number” buttons 556 that correspond to thechip being used. If the position data and component selection has beenproperly made, the user may then select the “check save” button 546 atthe top of the screen which saves the data to the memory storage unit ofthe controller 28 or other suitable device. This same procedure may beapplied to the teaching of position data of the pin tool head assemblyand pin tools 68 thereof, as well as the position of other components,by using other buttons on the screen. For example, position data for the2-d bar code on a chip may be taught by using the “bar code reader”button 558, and the camera by using the “camera” button 560. Theposition data related to the calibration material vessel 256 may betaught by using the “calibration vessel” button 562.

Once one or more position data sets have been taught to the controller28, there are other features on the deck plate screen that allow a userto carry out basic functions on an as needed basis. For example, a usermay initiate a wash cycle by touching “wash cycle” button 564, a rinsecycle by touching “rinse cycle” button 566 or a dry cycle by touching“dry cycle” button 568. A “calibration vessel home” button 570 may beused to move the pin tool head assembly 64 to the calibration vessel256. A “pin tool selection” button 572 may be used to select or togglebetween various pin tool array configurations, such as a single pintool, 6 pin tool array or 24 pin tool array as well as others. A“configuration screen” button 574 may be touched by a user to jump tothe configuration screen, a “motion screen” button 576 may be used tojump to the motion screen and a “vision screen” button 575 may be usedto jump to the vision screen shown in FIG. 34.

The vision screen includes controls that allow a user to turn theimaging camera 132 on and off and move the camera to a desired positionmanually with a set of jog arrows 580 which may be toggled between largemovement steps and small movement steps with a “toggle” button 582. Thelive video image block 584 allows the user to see the work surface 22and functional elements and components thereof through the imagingcamera lens while the camera is being positioned with the jog arrowbuttons 580. The vision screen may also be used in conjunction with thedeck plate screen for manual teaching of positions and relativepositions of the pin tool head, bar code reader and imaging camera withrespect to the work surface 22 and functional elements thereof. Worksurface components may be viewed on the video image block 584 andaligned with a cross hair centering reticle 586 positioned in the centerof the field of view of the imaging camera so that the position of theviewed and aligned component may be know with regard to the position ofthe imaging camera 132. If the position of the center of field of viewof the imaging camera is know with respect to other components of thedevice 10, this positioning data may be stored or otherwise used tocalculate the position of other components. If the imaging camera isaligned with a component at a position that is useful to be taught tothe controller 28, the “check” button 532 may be selected to take theuser to the deck plate screen discussed above for manual teaching ofposition as discussed above.

A top row on the vision screen includes the exit button 404, statusbutton 402, and help button 406 that may have he same functions asdiscussed above. Also on the top row of the vision screen are an “open”button 442 and a “save” button 444. The open button 442 allows a user toopen a predetermined set of method transfer parameters and the savebutton 444 allows a user to save a predetermined set of method transferparameters. A “configuration” button 588 allows a user to set a varietyof imaging parameters such as exposure, gain and further adjustment ofjog movement parameters such as the length of the large and smallmovement jog steps. The safety interlock indicator 590 indicates whetherthe safety interlock switch is engaged or disengaged. An “illuminator”button 592 toggles an illumination light source for the imaging camera132 on and off. A “zoom” button 594 zooms the field of view in the liveimage block 584 in and out and a “video on” button 596 toggles theimaging camera 132 on and off.

A set of “chip type” buttons 598 allows a user to select the type ofchip 274 being imaged or otherwise used on the work surface 22. Aselection may be made between a 96 site chip and a 384 site chip. A setof selection arrows 600 allow a user to choose from a menu ofpredetermined image processing algorithms 601 which may be used toconfirm the position of the imaging camera relative to a feature orcomponent of interest. Examples of the algorithms include a 2-d bar codealgorithm, an align a 96 site chip algorithm, an align a 384 site chipalgorithm, an align a 96 well microtiter plate algorithm, an align a 384well microtiter plate algorithm, a calibrate pins algorithm, a calibratepixels algorithm, and a volume check algorithm. The calibrate pinsalgorithm determines the center of the field of view of the imagingcamera with respect to the position of a particular pin tool, such asthe A1 positioned pin tool. The calibration of pixels algorithm uses theknown distance between two fiducial marks on a chip 274 to calculate thenumber of pixels of the imaging camera per millimeter on the plane ofthe work surface. The “measure” button 602 may be used or selected inorder to initiate a selected algorithm process once the camera has beenpositioned in a desired location. The “run” button 604 may be selectedto move the pin tool head assembly, bar code reader or camera to aposition on the work surface 22 corresponding to the algorithm selectedto be run.

In addition to embodiments described above, other similar embodiments,such as those discussed below, may also be used in the same or similarmanner as discussed above. For some embodiments, a pin protection blocktool assembly for selectively displacing at least one pin tool 68 of apin tool head assembly 64 of a robotic sample transfer device 10 may beused. Using the pin protection block tool allows the user to select anynumber of active pin tools by selective deactivation of the pin toolsnot being used in the standard 24 pin tool head 64. For instance, if theuser wants only a single pin tool active, the user may use the pinprotection block tool assembly in conjunction with a pin tooldisplacement block having a single pin configuration to selectivelydeactivate all but one of the pin tools 68 (e.g., deactivate 23 of 24).The pin protection block tool assembly, as shown in FIGS. 37A-37C, isused for upwards axial displacement of the pin tools 68 and pin toolcollars 143 within the pin tool head assembly 64 prior to insertion of apin tool displacement block. The pin protection block tool assembly hasbody 610 which is substantially rectangular in shape and has raisededges 614 which act as a hard stop to the downward movement of the lowersurface, which in turn may prevent the user from over compressing thepins and damaging the pin array and holder, while allowing adequate roomfor inserting a pin tool displacement block (also referred to as a pintoo displacement comb) of pin tool head assembly 64 of robotic sampletransfer device 10. The pin protection block tool assembly has a topsurface and a bottom surface which is substantially parallel to the topsurface, and a plurality of non penetrating cylindrical bores machinedinto the block body, arranged with a predetermined regular spacingconfigured to correspond to regular spacing of pin tools 68 of a pintool head assembly 64. At least two pins extending from or through thebottom surface of the pin protection block tool assembly are configuredto register the pin protection block tool assembly in fixed lateralalignment with the holes of the vacuum drying station 176. The pinsserve to secure the pin protection block tool assembly to the vacuumdrying station 176, for use in selectively displacing one or more pinsin the pin too head assembly 64. Pin protection block tool assembly body610 also has spacing element 612 which fits into the channel machinedinto vacuum drying station 176 (see FIG. 7) that allows properorientation and fitting of the pin protection block tool assembly forselectively displacing one or more pins in the pin too head assembly 64.Spacing element 612 acts as a keying feature such that the pinprotection block assembly may only be inserted in one orientation, thuspreventing the user from incorrectly mounting the pin protection blockassembly and potentially damaging the pin tools 68 or the pin tool head64. The pin protection block tool assembly embodiment may be machinedfrom a monolithic block of a strong stable material, such as polymers,such as Delrin®, composites and metals, such as stainless steel,aluminum, which may be anodized, and the like.

The regularly spaced cylindrical bores in the upper surface of the pinprotection block tool assembly may be of sufficient diameter to allow alower part of the tapered portion 158 and slotted tip 162 of pin toolshaft 142 to enter the opening, yet narrow enough for the upper taperedportion of pin tool shaft 142 to come to rest against the edge and innerwall surface of the cylindrical bores in the pin protection block toolassembly (see FIG. 42). The pin tools resting on an upper part of thetapered portion 158 of slotted pin too tip 162 may prevent damage to thelower slotted portion of the pin tool 68, by focusing downward pressureon the sturdier upper part of the tapered portion 158 of pin tool 68.The diameter of pin protection block tool assembly holes maybe in therange of about 0.01 to about 0.1 inches, and more specifically in therange of about 0.05 to about 0.06 inches in diameter. The depth of theholes in the pin protection block tool assembly maybe greater than thelength of the tapered portion of the pin tool shaft, such that when thepin tool head assembly 64 comes to rest on the raised edges 614 of thepin protection block tool assembly body 610, the pin tools 68 may besuspended above the bottom of the machined holes and the pin tools maybe held in place by contact an upper part of the tapered portion 158 ofpin tool shaft 142 and the edges of the cylindrical bores in the pinprotection block tool assembly body. The depth of the non-penetratingcylindrical bores of the pin protection block tool assembly may be inthe range of about 0.1 to about 1 inch and more specifically in therange of about 0.3 to about 0.4 inches in depth.

In some embodiments, the pin protection block tool assembly is used inconjunction with a plunger mechanism assembly, as shown in FIGS. 38A-38Band 39A-39B. The plunger mechanism assembly may be useful for downwarddisplacement of the z-axis carrier and pin tool assembly whichtranslates to upwards axial displacement of the pin tools 68, relativeto pin tool head 64, to allow insertion of various comb insert blocks,which allow the selective displacement of one or more pin tools 68 in apin tool head assembly 64. The plunger mechanism assembly includes acollar 620 and plunger handle 630.

Referring now to FIGS. 38A-38B, plunger mechanism collar 620 issubstantially cylindrical with a central concentric stepped cylindricalbore in the material of the collar. The plunger mechanism assemblyembodiment may be machined from a monolithic block of a strong stablematerial, such as polymers, such as Delrin®, composites and metals, suchas stainless steel, aluminum, which may be anodized, and the like. Theouter diameter 622 of the plunger mechanism collar may be in the rangeof about 0.5 to about 3 inches and more specifically in the range ofabout 1.5 to about 2 inches in diameter. The central concentric steppedcylindrical bore has two different diameters (624, 626), which whenviewed from a top down position assumes the configuration shown in FIG.38A. The larger of the two inner diameters 624 may be machined to adepth from the top of the collar in the range of about 1.20 to about1.45 inches, and more specifically about 1.35 to about 1.39 inches. Thediameter of this larger of the inner bores may be in the range of about0.1 to about 1 inch and more specifically in the range of about 0.4 toabout 0.6 inches. The smaller of the two diameters 626 may be formedfrom the bottom of the larger diameter to the bottom of the collarforming an opening with a diameter in the range of about 0.1 to about0.4 inches and more specifically in the range of about 0.23 to about0.27 inches in diameter. Plunger mechanism assembly collar 620 allowsfunctional coupling to both the plunger 630 of the plunger mechanismassembly and the threaded rod 118 of the z-axis translatable carrier 56,which carries pin tool assembly 64. In some embodiments plungermechanism collar 620 functions as an additional positional stop toprevent over compressing the axial springs 152 or the pin tool tips 156of the pin tools. In some embodiments plunger mechanism collar 620functions as a guide to prevent lateral displacement of the threadedshaft 118, thus minimizing the potential for damage to the z-axistranslatable carrier mechanism by bending or flexing threaded shaft 118,during axial displacement. In some embodiments plunger mechanism 620provides both functions.

Referring now to FIG. 39A-39B, plunger 630 of the plunger mechanismassembly may be configured to allow fitment into plunger mechanismassembly collar 620. Plunger 630 may be in the range of about 1 to about4 inches in height, and more specifically in the range of about 1.55 toabout 1.85 inches in height. Plunger 630 may be formed with a main shaft634 with a diameter in the range of about 0.3 to about 0.7 inches, andmore specifically in the range of about 0.4 to about 0.6 inches indiameter. This main shaft enlarges to a cylindrical plunger handle 632with a diameter in the range of about 0.5 to about 3.0 inches and morespecifically in the range of about 1.5 to about 2 inches in diameter.The base of the plunger handle shaft 634 contains a cylindrical bore 636with a diameter in the range of about 0.1 to about 0.4 and morespecifically in the range of about 0.23 to about 0.27 inches indiameter. The depth of cylindrical bore 636 may be in the range of about0.01 to about 0.2 inches and more specifically in the range of about0.08 to about 0.12 inches in depth. The plunger mechanism assemblyhandle 630 may be so configured to allow functional coupling to both theplunger mechanism assembly collar 620 and the threaded rod 118 of thez-axis translatable carrier 56, which carries pin tool assembly 64.

FIG. 38B is a cross sectional view of the central concentric steppedcylindrical bore of the plunger mechanism collar 620 which shows wherethe plunger handle 630 and the threaded rod 118 of z-axis translatablecarrier 56 are brought into functional coupling in the interior ofcollar 620 of the plunger mechanism assembly. In some embodiments theplunger mechanism assembly may be assembled and functionally coupled tothe threaded shaft 118 of z-axis translatable carrier 56 to enableupwards axial displacement of the pin tool tools 68, relative to the pintool head 64, to allow insertion of various comb insert blocks, enablingthe selective displacement of one or more pin tools 68 in a pin toolhead assembly 64. As described previously, the pin tool head assembly 64may be placed on a hard surface with the tips of the pin tools restingdirectly on the hard surface (see FIG. 18 and FIG. 19). For someembodiments the comb insert block assembly may be used to suspend thetips of the pin tools 68 over the machined cylindrical bores of the combinsert block assembly with the main shaft of the pin tools 68 supportingthe pin tools as the threaded collar 118 in functional contact with pintool head assembly 64 may be depressed using the plunger mechanismassembly functionally coupled to the threaded shaft 118 or z-axistranslatable carrier 56, causing the upwards axial displacement of thepin tool collar member 143, relative to the pin tool head 64. Use of thecomb insert block assembly reduces the possibility of damage to the pintools 68 by eliminating placing the tapered portion 158 and slotted tip162 of pin tool shaft 142 in direct contact with a hard surface.

As described previously, it may be desirable to selectively alter thenumber of pins being used in the pinhead tool 64, without physicallychanging out the pinhead tool. For some embodiments, a method forselectively displacing at least one pin tool 68 of a pin tool headassembly 64 of a robotic sample transfer device 10 may optionallyinclude providing a pin protection block tool assembly and a plungermechanism assembly in addition to the pin tool insert block. Such amethod embodiment may be initiated using the user interface 26 andnavigating the various programming controls of device 10. The commandsfor altering pin tool configuration are located in the “MaintenanceScreen” accessed from the main menu. Once in the “Maintenance Screen”,the “Change Insert” button may be selected to initiate the method forselectively displacing at least once pin tool 68 in the pin tool headassembly 64.

Upon program initiation, the pin tool head may be moved away from thevacuum drying station 176 of the cleaning and drying portion of device10, facilitating removal of any vacuum plates or calibration wells, andallowing positioning of the pin protection block tool assembly. The pinprotection block tool body 610 of the pin protection block tool assemblymay be positioned using the aligning element 612 and pins 616. Pins 616are reversibly operationally coupled with holes in the vacuum dryingstation 176. Once the pin protection block tool assembly is in place,“Continue” may be selected using the user interface 26 and device 10moves pin tool head 64 over the pin protection block tool assembly. Pintool head 64 is automatically lowered approximately 5 mm, placing thenarrowest part of the tapered portion 158 of pin tools 68 within thecylindrical bores of the pin protection block tool assembly. The usermay then functionally couple the plunger mechanism to the threaded shaft118, and apply downward pressure to compress the pin tool head 64 theremaining distance to bring the bottom plate 139 of pin tool head 64 incontact with pin protection block assembly raised edges 614, asillustrated in FIG. 42. FIG. 42 illustrates the functional coupling ofthe comb insertion block assembly, pin tool head 64, threaded shaft 118,Z-axis step motor 126, y-axis translatable carrier 62, z-axistranslatable carrier, plunger mechanism collar 620, and plunger 630, allused in concert to allow selective displacement of pin tools 68 in a pintool head 64. Downward pressure, as shown by the downward arrow in FIG.42, may be applied to plunger 630 through plunger handle 632 whichpushes pin tools 68 against the pin protection block tool assembly whichin turn serves to push the pin tool collars 143 up, relative to pin toolhead 64, allowing the insertion of a pin tool insert comb. After the pintool comb insert (336 or 360) is inserted, the plunger mechanismassembly may be removed, which allows the pin tool head to come back toa relaxed state. “Continue” may be selected on the user interface 26,and device 10 completes the pin tool selection program. In someembodiments, device 10 may provide the user with visual prompts. In someother embodiments device 10 may provide the user with auditory prompts.In yet other embodiments, device 10 may provide the user with videoclips showing the procedure being performed. In some embodiments device10 may provide a combination of visual prompts, auditory prompts, andvideo clips to aid the user in completing the pin tool displacementblock insert procedure.

As previously described and illustrated in FIGS. 20A-20D and FIGS.21A-21D, pin tool displacement blocks may be used that enable theselective displacement of one or more pin tools 68 in a pin tool headassembly 64. FIGS. 35A-35D and FIGS. 36A-36D illustrate embodiments ofpin tool displacement blocks. Pin tool comb 336′ and 360′ of FIGS.35A-35D and 36A-36D may have features, dimensions, or materials that arethe same or similar to those of 336 and 360 in FIGS. 20A-20D and21A-21D. Additionally the methods useable for insertion of thepreviously described and illustrated pin tool displacement blocks maybethe same as the methods used to insert the additional embodiments of thepin tool displacement blocks.

Referring now to FIG. 35A-35D, in some embodiments a pin tool combinsert allowing the displacement of all but one pin tool 68 is provided.This embodiment of a pin tool displacement block (pin tool comb insert)has raised edges 339 which act as an orientation keying feature whichprevents the pin tool displacement block from being insertedincorrectly. That is, raised edges 339 may confer a unidirectionalorientation to the pin tool displacement block. Pin tool comb insert336′ may also be configured to have a chamfered forward upper edge toallow the user easier insertion into the pin tool head 64.

Referring now to FIG. 36A-36D, in some embodiments a pin tool combinsert allowing the displacement of all but six pin tools 68 isprovided. This embodiment of a pin tool displacement block (pin toolcomb insert) has raised edges 363 which act as an orientation keyingfeature which prevents the pin tool displacement block from beinginserted incorrectly. That is, raised edges 363 may confer aunidirectional orientation to the pin tool displacement block. Pin toolcomb insert 360′ may also be configured to have a chamfered forwardupper edge to allow the user easier insertion into the pin tool head 64.

While pin tool displacement blocks have been described herein forapplications that selectively displace all but one or all but 6 pintools, pin tool numbers other than 1, 6 or 24 maybe used. The number andpattern of pin tools selectively displaced and thereby inactivated maybe 1, 2, 3, 4, 5, 6, 7 . . . up to 23, when using a 24 pin tool head.This may be achieved by an alternative configuration of pin tooldisplacement blocks, and the disclosure herein is not meant to limit theembodiments contemplated to 1, 6, or 24 active pin tools 68.

In some embodiments where the number of pin tools being actively usedhas been selectively altered, a dry station plate assembly may beprovided that may be configured to correspond to the pattern of the pintools selected to be active. The dry station plate assembly allows forselective use of the vacuum drying station 176 vertical holes 178 asdrying orifices. This allows the user to direct the vacuum to only thosepin tools 68 actively being used in any particular application. The drystation plate assembly may be machined from a monolithic block of astrong stable material, such as polymers, such as Delrin®, compositesand metals, such as stainless steel, aluminum, which may be anodized,and the like. The dry station plate assembly may also be cut or machinedfrom Lucite®, polycarbonates, acrylic and the like. Dry station plateassemblies for any number of openings corresponding to a desired numberof selectively activated pin tools 68 are contemplated herein as well asthe embodiments described below. In general the dry station plateassembly (640, 650) may be substantially rectangular in shape, the sizeand shape corresponding with the size and shape of pin tool head 64. Theheight of the dry station plate assembly body (642, 652) may be in therange of about 0.01 to about 1 inch, more specifically in the range ofabout 0.1 to about 1 inch and most specifically be in the range of about0.2 to about 0.5 inches in height. The dry station plate assemblies mayhave at least 3 holes machined through the body to allow insertion ofseating pin dowels, the holes being of sufficient diameter to allow theuse of pin dowels (644, 654) that fit within the nominal diameter of thevacuum dry station 176 vertical holes 178, and allow functional couplingof the dry station plate assembly to the vacuum drying station. The useof dry station plate assemblies may reduce the waste of vacuum in thevacuum holding tank by channeling vacuum to only the openings 178 thatcorrespond to active pin tools 68, and blocking off all other openingsthrough which vacuum might be wasted. Additionally, if the unused holesare not blocked using the dry station plate assemblies, all vacuum flowwill be through the unblocked holes and minimal flow will be through theholes containing pin tools. This may cause the pins to not besufficiently dried, which in turn may lead to cross contamination ofsamples.

Referring now to FIGS. 40A-40C, in some embodiments a vacuum dryingstation plate assembly 640 which blocks all but one vertical hole 178 inthe vacuum drying station 176 is provided. Vacuum drying station plateassembly 640 includes plate body 642, pin dowels 644 and pin toolopening 646. The embodiment of dry station plate assembly 640 may beused in conjunction with the pin tool insert comb that selectivelydisplaces or deactivates all but one pin tool 68.

Referring now to FIGS. 41A-41C, in some embodiments a vacuum dryingstation plate assembly 650 which blocks all but six vertical holes 178in the vacuum drying station 176 is provided. Vacuum drying stationplate assembly 650 includes plate body 652, pin dowels 654 and pin toolopenings 656. The embodiment of dry station plate assembly 650 may beused in conjunction with the pin tool insert comb that selectivelydisplaces or deactivates all but six pin tools 68.

In general, a wide variety of techniques can be implemented consistentwith the principles the invention and no attempt is made herein todescribe all possible techniques. With regard to the above detaileddescription, like reference numerals used therein refer to like elementsthat may have the same or similar dimensions, materials andconfigurations. While particular forms of embodiments have beenillustrated and described, various modifications can be made withoutdeparting from the spirit and scope of the embodiments of the invention.Accordingly, it is not intended that the invention be limited by theforgoing detailed description.

1. A robotic sample transfer device, comprising: a substantiallyhorizontal work surface including a plurality of functional elementsconfigured for small sample processing; a three axis robotic positioningassembly having a fixed mount portion secured in fixed relation with thework surface, a translatable carrier configured to be translatable inthree axes with respect to the fixed mount portion and working surfaceand having a stepper motor corresponding to each axis and at least onelinear encoder assembly configured to generate position data for atleast one axis; at least one pin tool coupled to the translatablecarrier; and a controller in communication with the stepper motors ofeach of the three axes of the three axis robotic positioning assemblyand the at least one linear encoder assembly.
 2. The sample transferdevice of claim 1 further comprising a housing disposed about the worksurface, three axis robotic positioning assembly and controller.
 3. Thesample transfer device of claim 2 further comprising a graphic userinterface on an exterior of the housing and operatively coupled to thecontroller for providing user input to the controller.
 4. The sampletransfer device of claim 1 wherein the three axes of the three axisrobotic positioning assembly are substantially orthogonal to each other.5. The sample transfer device of claim 1 wherein the three axis roboticpositioning assembly further comprises a bar code reader.
 6. The sampletransfer device of claim 1 wherein the three axis robotic positioningassembly further comprises an imaging camera translatable in at leasttwo axes and operatively coupled to an image processor.
 7. The sampletransfer device of claim 1 wherein the controller comprises at least oneprocessor which is disposed within the housing at a level which is abovethe level of the work surface.
 8. A robotic sample transfer device,comprising: a housing; a substantially horizontal work surface disposedwithin the housing; a three axis robotic positioning assembly disposedwithin the housing having a fixed mount portion secured in fixedrelation with the work surface and a translatable carrier membertranslatable in three different axes with respect to the fixed mountportion and work surface; at least one pin tool coupled to thetranslatable carrier having a shaft and a sample reservoir in a distalend of the shaft; a plurality of functional elements disposed on thework surface having a nominal upper surface at substantially the sameheight; and a controller operatively coupled to the three axis roboticpositioning assembly.
 9. The sample transfer system of claim 8 furthercomprising an imaging camera movable in at least the x-y planesubstantially parallel to the work surface and having a shallow range offocus and focused at the nominal upper surface of the functionalelements.
 10. The sample transfer device of claim 8 wherein thefunctional elements comprise a vacuum drying station, a fluid rinsestation, a microtiter plate having an array or regularly space samplesupply wells and a chip having an array of regularly spaced sampledeposition sites.
 11. The sample transfer device of claim 8 furthercomprising a pin tool head assembly having an array of regularly spacedpin tools secured to the translatable carrier and wherein the vacuumdrying station includes a plurality of regularly spaced vacuum dryingports corresponding to the spacing of the pin tools of the pin tool headassembly, the fluid rinse station includes individual rinse tubescorresponding to each of the pin tools of the array of regularly spacedpin tools of the pin tool head assembly.
 12. The sample transfer deviceof claim 10 further comprising a self-leveling gravity fed ultrasoniccleaning well and an ultrasonic cleaning fluid reservoir having a supplyport configured to couple into fluid communication with the ultrasoniccleaning well when coupled to an inlet port of the ultrasonic cleaningwell and be substantially sealed when the removed from the inlet port ofthe ultrasonic cleaning well.
 13. The sample transfer device of claim 10wherein the ultrasonic cleaning fluid reservoir further comprises a ballvalve which is configured to seal the supply port when the fluidreservoir is removed from the inlet port of the ultrasonic cleaningwell.
 14. The sample transfer device of claim 8 wherein the controllercomprises at least one processor which is disposed within the housing ata level which is above the level of the work surface.
 15. An integratedrobotic sample transfer device, comprising: a housing; a three axisrobotic positioning assembly disposed within the housing having a fixedmount portion, a translatable carrier translatable in three axes withrespect to the fixed mount portion and working surface and having astepper motor corresponding to each axis and at least one linear encoderassembly for generating position data for at least one axis of thetranslatable carrier; a pin tool head assembly secured to thetranslatable carrier member having an array of regularly spaced pintools with sample reservoirs disposed in the distal ends thereof andconfigured for axial displacement relative to a pin head body secured tothe translatable carrier of the three axis robotic positioning assembly;a substantially horizontal work surface disposed within the housing andsecured in fixed relation to the fixed mount portion of the three axispositioning assembly and having a fluid rinse station, a vacuum dryingstation including a plurality of regularly spaced vacuum drying portscorresponding to the regular spacing of the array of pin tools, aself-leveling ultrasonic cleaning well and a microtiter plate mountblock configured to releasably secure a sample well; a controllerincluding a processor disposed within the housing at a position which isabove the level of the work surface; a rinse fluid supply tank in fluidcommunication with the fluid rinse station and disposed within thehousing; a waste fluid tank in fluid communication with an overflowbasin of the fluid rinse station and disposed within the housing; avacuum source in fluid communication with the vacuum drying station; andan ultrasonic cleaning fluid reservoir in fluid communication with aself-leveling ultrasonic cleaning well.
 16. The sample transfer deviceof claim 15 wherein in the ultrasonic cleaning fluid reservoir comprisesa gravity feed reservoir having a supply port configured to couple intofluid communication with the ultrasonic cleaning well when coupled to aninlet port of the ultrasonic cleaning well and be substantially sealedwhen the removed from the inlet port of the ultrasonic cleaning well.17. The sample transfer device of claim 15 further comprising a rinsefluid supply tank fluid level indicator.
 18. The sample transfer deviceof claim 15 further comprising a rinse fluid supply pump disposed withinthe housing, in fluid communication with the rinse fluid supply tank andfluid rinse station and configured to pump rinse fluid from the rinsefluid supply tank to the fluid rinse station.
 19. The sample transferdevice of claim 15 further comprising a waste fluid tank fluid levelindicator.
 20. The sample transfer device of claim 15 further comprisinga vacuum drying supply tank in fluid communication with the vacuumdrying ports of the vacuum drying station.
 21. The sample transferdevice of claim 20 further comprising a vacuum pump in fluidcommunication with the vacuum drying supply tank.
 22. The sampletransfer device of claim 15 wherein a nominal upper surface of the fluidrinse station, nominal upper surface of the vacuum drying station,nominal upper surface of the ultrasonic cleaning well, nominal uppersurface of a chip disposed in the chip mount block and microtiterplate/sample well mounted in the sample well mount blocks all being atsubstantially the same z-axis level.
 23. The sample transfer device ofclaim 15 further comprising an imaging camera and image processingcontroller.
 24. The sample transfer device of claim 15 furthercomprising a bar code reader head and bar code reader processor incommunication with the bar code reading head and controller.
 25. Thesample transfer device of claim 15 wherein the fluid rinse stationcomprises an array of regularly spaced individual rinse tubes having aregular spacing corresponding to the regular spacing of the pin tools ofthe pin tool head assembly.
 26. The sample transfer device of claim 15further comprising a door on the housing covering an opening to aprocessing chamber disposed within the housing.
 27. The sample transferdevice of claim 15 wherein the controller comprises an assembly ofelectronics and logic circuits which are disposed within the housing ata position which is above the level of the work surface.
 28. The sampletransfer device of claim 15 further comprising a universal power supplyin communication with the controller that produces a constant outputvoltage with varied input voltage to allow device to operate in varyingcountries.
 29. The sample transfer device of claim 15 wherein the entiredry weight of the device is less than about 150 pounds.
 30. The sampletransfer device of claim 15 further comprising a graphic user interfacedisposed on an outer surface of the housing and in communication withthe controller.
 31. The sample transfer device of claim 15 furthercomprising a humidity sensor disposed within the processing chamber ofthe device and in communication with the controller which is configuredto sense the humidity within the processing chamber.
 32. The sampletransfer device of claim 31 further comprising closed loop feedback fromthe humidity sensor with the controller in conjunction with a humiditycontrol device for maintaining a substantially constant humidity withinthe processing chamber.
 33. The sample transfer device of claim 15further comprising a temperature sensor disposed within the processingchamber of the sample transfer device in communication with thecontroller which is configured to sense the temperature within theprocessing chamber.
 34. The sample transfer device of claim 33 furthercomprising closed loop feedback from the temperature sensor with thecontroller and a temperature control device for maintaining asubstantially constant temperature within the processing chamber.
 35. Amethod of registering the position of a pin tool head assembly of arobotic sample transfer device relative to sample deposition sites on achip, comprising: providing a robotic sample transfer device having awork surface with a plurality of functional elements with a nominalupper surface at substantially the same level and a three axispositioning system with a camera and pin tool head assembly secured to atranslatable carrier thereof; imaging the nominal upper surfaces offunctional elements disposed on work surface with the camera; processingthe image data of the nominal upper surfaces of the functional elementsfrom the camera to determine the approximate position of the pin toolhead assembly relative to the functional elements; using the approximateposition data to move the camera to a first chip having an array ofregularly spaced sample deposition sites and an array of regularlyspaced fiducial marks disposed between the sample deposition sites;imaging fiducial marks on the first chip; processing the image data offiducial marks on the first chip; obtaining feedback regarding aposition of the pin tool head assembly from linear encoders of threeaxes of a three axis robotic positioning system; comparing encoderfeedback with image processing feedback and look up table data todetermine the precise position of the pin tools of the pin tool headassembly with respect to the sample deposition sites on the first chip.36. The method of claim 35 further comprising repeating the process formultiple chips.
 37. The method of claim 35 wherein the precise positionof the pin tools of the pin tool head assembly with respect to thesample deposition sites on the first chip is determined to within about1 micron to about 10 microns.
 38. A method of dispensing calibrationmaterial onto a chip, comprising: providing a chip having a first arrayof regularly spaced sample deposition sites disposed on a substantiallyflat working surface thereof and at least one sample deposition site forreceiving calibration material which is also disposed on the flatworking surface of the chip and which is off pitch with respect to theregular spacing of the first array of regularly spaced sample depositionsites of the chip; providing a robotic sample transfer device having apin tool head assembly with an array of regularly spaced pin toolshaving distal ends which are substantially coplanar in a relaxed stateand which have a regular spacing which is the same as the regularspacing of the first array of sample deposition sites or an integermultiple thereof and configured to align with the array of regularlyspaced sample deposition sites of the chip or a subset thereof; loadingsample reservoirs of the array of regularly spaced pin tools of therobotic sample transfer device with calibration material; dispensingcalibration material from the pin tools of the robotic sample transferdevice to the at least one sample deposition site for receivingcalibration material such that the pin tools which are not aligned withsample deposition sites for receiving calibration material are off pitchwith respect to the first array of regularly spaced sample depositionsites of the chip and do not contact any of the regularly spaced sampledeposition sites of the first array.
 39. The method of claim 38 whereinthe chip comprises a second array of regularly spaced sample depositionsites for receiving calibration material sample which are off pitch withrespect to the first array of regularly spaced sample deposition sitesand further comprising dispensing calibration material from pin tools ofthe robotic sample transfer device to the second array of sampledeposition sites for receiving calibration material such that the pintools which are not aligned with sample deposition sites for receivingcalibration material of the second array are off pitch with respect tothe first array of regularly spaced sample deposition sites of the chipand do not contact any of the regularly spaced sample deposition sitesof the first array.
 40. The method of claim 38 wherein the first arrayof regularly spaced sample deposition sites comprises an array ofregularly spaced mass spectrometry sample deposition sites.
 41. A pintool displacement block for selectively displacing at least one pin toolof a pin tool head assembly of a robotic sample transfer device in anaxial direction, comprising: a block body having a bottom surface and aplurality of parallel slots formed into the block body portionsubstantially perpendicular to the bottom surface with a predeterminedregular spacing configured to correspond to regular spacing of pin toolsof a pin tool head assembly and having a transverse dimension sized toallow easy movement of a width of a nominal shaft of the pin tools inthe slots but restrictive of movement of an enlarged portion of theshaft of the pin tools; and at least one relieved portion in a slotwhich has a transverse dimension sized to allow easy downward movementof the enlarged portion of a pin tool shaft which is greater than thetransverse dimension of the slot and which extends from a top surface ofthe block body towards the bottom surface.
 42. The pin tool displacementblock of claim 41 wherein the at least one relieved portion terminatesat a stop surface which is spaced from the bottom surface.
 43. The pintool displacement block of claim 41 wherein the at least one relievedportion extends completely from the top surface to the bottom surfaceand is configured to allow the enlarged portion of a pin tool shaft topass completely through the block body.
 44. The pin tool displacementblock of claim 41 wherein the relieved portion is configured tomechanically capture the enlarged portion of a pin tool disposed thereinin a lateral direction.
 45. The pin tool displacement block of claim 41wherein the enlarged portion of a shaft of a pin tool comprises a collarmember and the stop surface of the at least one relieved portion isconfigured to prevent axial movement of the collar member andmechanically capture a collar disposed therein member to prevent lateraldisplacement of the block body when the block is deployed in a pin toolhead assembly.
 46. The pin tool displacement block of claim 41 whereinthe top surface and bottom surface of the block body are substantiallyflat and substantially parallel to each other.
 47. The pin tooldisplacement block of claim 41 wherein the block body comprises an inertmaterial.
 48. The pin tool displacement block of claim 46 wherein theinert material comprises Delrin.
 49. The pin tool displacement block ofclaim 41 further comprising a handle member secured to the block body.50. The pin tool displacement block of claim 41 having a reversibleconfiguration wherein when the block is oriented in a first direction afirst pin or set of pins is active and when oriented a second way asecond pin or set of pins is active which is different from the firstset.
 51. The pin tool displacement block of claim 50 wherein the firstdirection is about 180 degrees from the second direction.
 52. A methodfor selectively displacing at least one pin tool of a pin tool headassembly of a robotic sample transfer device, comprising: providing apin tool displacement block including a block body having a bottomsurface and a plurality of parallel slots formed into the block bodyportion substantially perpendicular to the bottom surface with apredetermined regular spacing configured to correspond to regularspacing of pin tools of a pin tool head assembly and having a transversedimension sized to allow easy movement of a width of a nominal shaft ofthe pin tools in the slots but restrictive of movement of an enlargedportion of the shaft of the pin tools, and at least one relieved portionin a slot which has a transverse dimension sized to allow easy downwardmovement of the enlarged portion of a pin tool shaft which is greaterthan the transverse dimension of the slot and which extends from a topsurface of the block body towards the bottom surface; displacing anarray of pin tools of a pin tool head assembly by depressing the pintools against a flat surface; deploying the pin tool displacement blockinto the pin tool head assembly such that the parallel slots of the pintool displacement block slide over rows of the array of pin tools of thepin tool head assembly; and allowing the pin tools to return to arelaxed state by retracting the pin tool head assembly from the flatsurface with at least one of the pin tools axially displaced in therelaxed state.
 53. A method of dispensing calibration material onto achip, comprising: providing a chip having an array of regularly spacedsample deposition sites disposed on a substantially flat working surfacethereof and at least one sample deposition site for receivingcalibration material which is also disposed on the flat working surfaceof the chip; providing a robotic sample transfer device having a pintool head assembly with an array of regularly spaced pin tools havingdistal ends which are substantially coplanar in a relaxed state andwhich have a regular spacing which is the same as the regular spacing ofthe first array of sample deposition sites or an integer multiplethereof and configured to align with the array of regularly spacedsample deposition sites of the chip or a subset thereof; axiallydisplacing at least one of the pin tools of the pin tool head assemblywith a pin tool displacement block; loading a sample reservoir of atleast one un-displaced pin tool of the robotic sample transfer devicewith calibration material; dispensing calibration material from the atleast one un-displaced pin tool of the robotic sample transfer device tothe at least one sample deposition site for receiving calibrationmaterial such that the pin tools which are displaced by the pin tooldisplacement block do not contact the chip.
 54. The method of claim 53wherein the array of regularly spaced sample deposition sites comprisesan array of regularly spaced mass spectrometry sample deposition sites.